Canopy & Co. Ltd, London 360° Life Sciences Investment ... · PDF file• Phase 3...

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JUNE 19, 2014

DATA USD

Price (06/18/2014): Price Change 1D: Market Cap: EV: Net Cash: Funding (since inception): IPO: Market Sector Index: Founded: Employees: Sector: IP (patents): Alliances:

1.13 -5.83%

195.63m 178.98m

16.65m 105m 2002

NBI 2002

4 FTEs Drug Development

28 2+

OWNERSHIP

Share Outstanding : Insiders: Institutionals: Free Float:

173,125,972 8.86% 0.51%

93%

CATALYSTS

HOT • Phase 3 initiation (estim. Q4’14) with SPA • PH-10 co-dev/out-licensing deal • Cash inflow with non strategic disinvestment

COLD

• Negative FDA reply for PV-10 Phase 3 SPA • Positive clinical results of competitive drug

candidates in metastatic melanoma

PRICE PERFORMANCE

RESEARCH TEAM CONTACT

Gerard Pontonnier, PharmD Managing Director, Research Supervisor

+44 (0)203 102 7705 [email protected]

FDA Denied to Grant a BTD for PV-10 in Melanoma

At the end of a 60-day regulatory period, FDA denied to grant a Breakthrough Therapy designation (BTD) to PV-10. We don’t consider this disappointing letter as a redhibitory “red flag” for PV-10 pathway to go forward in clinical development for an NDA. FDA asked for more data to to demonstrate a substantial efficacy improvement compared to the current therapies based on clinically significant endpoints. Since the FDA launched this new BTD status, CDER did not show pretty good statistics to help drug developers: only 28% (44) of requests were granted and 47% (73) denied (July 2012 - May 2014). This designation, in add to the accelerated pathways (Fast Track, Accelerated Access, Priority Review), is granted to drug candidates intented to treat serious/life threatening conditions with early clinical data demonstrating a susbtantial improvement on one or more endpoints compared to the standard of care.

Moving Forward to Phase 3 ASAP!

In the last conference call held during ASCO annual meeting (June 3), PVCT Leadership highlighted next steps for PV-10 development plan with an initiation of a Phase 3 trial to occur on H2 2014 (we estimate a reasonable timing not early as Q4). This randomized, controlled trial will enroll 210 patients with unresectable locally advanced cutaneous melanoma. It will evaluate PV-10 versus systemic chemotherapy (not yet disclosed) in patients who have disease limited to cutaneous /subcutaneous sites and have failed or are ineligible for systemic immunotherapy. Endpoints will include progression free survival (PFS) (by RECIST 1.1), complete response rate (CRR) (by RECIST 1.1), overall survival (OS) and exploratory assessment of patient reported outcomes related to lesion pain and other melanoma symptoms. Regarding the clinical investigator sites, PVCT plans to select first US/AUS eligible patients always in expanded access and compassionate program to accelerate the enrollment. We anticipate that PVCT will apply for a Special Protocol Assessment (SPA) to accelerate the Phase 3 start.

Conference call, to be held today, June 19/4PM EDT, will certainly provide more details on the Phase 3 trial design, development plan and Company roadmap for the coming months. We will be also attentive to partnership strategy for PV-10/PH-10.

DISCOVERY

360°

Canopy & Co. Ltd, London Life Sciences Investment Research

NYSE-MKT: PVCT

Provectus Biopharmaceuticals

ASCO 2014: MELANOMA UPDATES ASCO Annual Meeting was an opportunity to take stock of Melanoma therapeutic advances. PVCT PV-10 clinical data were updated in two presentations at the poster highlights session. Today, we are waiting for the PVCT Conference Call to get more details on the Phase 3 design, short term clinical development and regulatory pathways. PVCT is still on the road for a challenging run in Melanoma cure.

CANOPY DISCOVERY 360° NOTE IS NOT SPONSORED BY THE ISSUER AND PUBLISHED WITHOUT ANY COMMITMENT TO BE UPDATED.

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http://www.canopyandco.co.uk/assets/CDER_BTR_Stats_May052014.pdf

http://www.pvct.com/pressrelease.html?article=20140612

PROVECTUS BIOPHARMACEUTICALS – NYSE-MKT: PVCT JUNE 19, 2014 w

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ASCO 2014: PVCT Update on Promising Phase 2 Data PVCT PV-10 data were updated at the ASCO annual meeting in Chicago (May 30-June, 3) with 2 presentations in “Melanoma/Skin Cancers” poster highlights session. The first one (#9027), "Efficacy of intralesional Rose Bengal in patients receiving injection in all existing melanoma in phase II study PV-10-MM-02" was presented by Sanjiv S. Agarwala, MD, of the St. Luke's Cancer Center (PA) and the second one (#9028), "Assessment of immune and clinical efficacy after intralesional PV-10 in injected and uninjected metastatic melanoma lesions", by Amod A. Sarnaik, MD, of Moffitt Cancer Center (FL). The ASCO meeting is the annual oncology research “showroom” and “think tank” for the pharma industry to present the latest cancer pipeline data and also to target oncology developers for potential partnerships. (Abstract #9027) Update on single-arm, multi-center Phase 2 trial of Rose Bengal disodium (PV-10) in 80 refractory cutaneous melanoma patients. Refractory patients received PV-10 into up to 20 cutaneous and subcutaneous lesions up to 4 times over a 16-week period and were followed for 52 weeks. Primary endpoint, ORR was assessed by RECIST in up to 10 injected lesions. Secondary endpoints included assessment of DR, ORR of untreated bystander lesions, OS and AEs. In a 28-patient subgroup receiving PV-10 in all existing melanoma lesions, ORR was 71% (CI 51-87%) with 50% CR (CI 31-69%). In 54 patients (previous 28 patients plus 26 patients with uninjected disease limited to bystanders), CR was 64% (achieved in 232/363 injected lesions): single injection for 121 lesions, 2 injections for 84 lesions, 3 injections for 22 lesions and 4 injections for 5 lesions. CR was also achieved in 10/28 uninjected bystander lesions. Overall, PV-10 was well tolerated. 41/80 ITT patients met the primary endpoint of OR (CR+PR) in their injected target lesions (51% ORR, CI 40-63%, 25% CR). This trial starting in 2007 was completed in June 2012 (data poster ESMO Oct. 2012). (Abstract #9028) Data presented on an ongoing Phase 1 evaluating immune and clinical efficacy of Rose Bengal disodium (PV-10) in patients with injected and uninjected metastatic melanoma lesions. Enrolment targets 8 patients with dermal and/or subcutaneous lesions. Intra-lesion PV-10 injection achieved a pathologic CR in the post-treatment biopsies of both PV10-injected and uninjected study lesions in 50% patients (4), and all 8 had at least partial regression of the injected lesion. Intra-lesion PV-10 injection was associated with an increase in circulating CD3+/CD8+ T cells. 75% patients (6) had metastatic disease refractory to YERVOY® ipilimumab, anti-PD-1 and/or ZELBORAF® vermurafenib regimens.

This ASCO event is an opportunity to compare PVCT PV-10 data to other big Bio/Pharma leaders and SMEs presentations in Melanoma therapy approaches. We have selected about thirty key clinical trial updates that reflect Melanoma research trends particularly on advanced/metastatic stages. It is clear that unique thinking does not exist in research for unmet medical needs: PVCT PV-10 is one challenging therapeutic approach - with a well balanced benefit/risk - supported by encouraging data in this Melanoma pipeline.

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CANOPY & CO. LTD DISCOVERY 360° - A CANOPY VIEW PAGE 2

http://meetinglibrary.asco.org/content/132320-144

http://www.pvct.com/publications/PVCT-ESMO-2012-Poster.pdf



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Market CapEV 91%

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PVCT STOCK PERFORMANCE

Price Change 52W 71%Price Change 1M -64%Price Change 3M -50%Price Change 1W -5%Avg Daily Vol 1W 3,275,960Avg Daily Vol 1M 3,066,350Avg Daily Vol 3M 1,481,510Avg Daily Vol 52W 1,222,974

PVCT 1M CHART

What About Melanoma Therapy Costs? As regulators like FDA are also thinking in terms of cost effectiveness for new drug approval, PV-10 could be one treatment option of the therapeutic new arsenal in combo regimen if PVCT provide sufficient data to reach the next clinical milestones. A recent comparative economic study on healthcare costs in patients with advanced metastatic melanoma explored the monthly regimen and adverse events (AEs) costs of available treatment options in a US managed care population (55 US health plans) between 2009-2012 (Chun-Lan Chang, J. Clin. Oncol. 32:5s 2014, ASCO 2014 #9007).

COMPARATIVE THERAPY COSTS IN PATIENTS WITH METASTATIC MELANOMA (2009-2012)

USD ipilumimab temozolomide vemurafenib paclitaxel dacarbazine Mean treatment cycle duration (median)

72 (73) days 87 (63) days 138 (124) days 100 (76) days 69 (54) days

Mean adjusted monthly costs

Therapy 65,313 17,885 17,223 16,941 16,123 AEs

Management 4,628 3,189 2,259 8,261 9,415

Total 69,941 21,074 19,482 25,202 25,538 After reviewing data for 541 metastatic melanoma patients (mean age: 57.5 years) with 49% having more than 3 sites of metastases, this study shows that the highest health care cost is reached with ipilumimab, YERVOY®: USD69,941 for a treatment cycle with AEs management. Interesting is also the cost of AEs management topping at 37% for dacarbazine. Safety/efficacy balance is a key point to take into account for physicians, managed care organizations in treatment options even if melanoma cure approach is a challenging debate facing to the cancer patients hope. We consider that PV-10 could be marketed with a lower range of treatment costs as 1/manufacturing costs are cheap, 2/R&D costs are not similar to Mabs like ipilumimab. For advanced melanoma patients, it opens valuable market options for PV-10 in combo treatment or alone, particularly in countries where access to cure is managed by therapy costs.

Assets Value

Over the last weeks, NY market feeling was particularly bearish for PVCT with the disappointing FDA letter arriving at the worst market timing for its uplisting to the NYSE MKT. PVCT is currently traded with an EV of USD178m based on a net cash of USD16.6m (10-Q, May 2014). With alternative funding options in place, Provectus manages the PV-10 cash runway into 2015 to move in Phase 3 by the end Q4 2014. Next short-term regulatory catalyst will be a positive SPA designation for the Phase 3 protocol assessment of PV-10, as “green light” to go forward. This would reverse the bearish stock opinion with a high volatility.

Investment Risk Profile

PVCT business model is focused on a small pipeline of drug candidates based on the Rose Bengal-based (RB) therapeutic approach. Near-term value creation is conditioned by a successful late stage development on PV-10, mainly in metastatic melanoma. The next critical short term milestone will be to reach Phase 3 stage after a positive protocol assessment by the FDA (SPA designation) in locally advanced cutaneous melanoma. To its benefit, RB has a long history of use as diagnostics agent in medicine with a well-researched safety profile. Malignant melanoma is a difficult disease to cure and many drug failures occurred over these last years. PVCT’s PV-10 can take advantage of this challenge as metastatic melanoma remains a high unmet medical need.




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Provectus management has implemented a virtual company model, as many young biopharma companies do, taking advantage in outsourcing R&D processes (e.g. clinical trials management with CROs, manufacturing…). The company head count is only 4 FTEs supported by external consultants. Any lack of coordination with PVCT service providers could affect adversely its R&D programs.

As a drug developer, the risk profile of PVCT is inherent of high R&D funding needs before generating revenues from partnering agreements, drug sales and reaching profitability. PVCT model favours co-development or out-licensing options which could generate first partnering income stream from pharma stakeholders.

PVCT has a sufficient cash balance (USD16m) to push forward its lead candidate PV-10 in Phase 3 and also access to additional cash resources with new equity/warrants offerings and equity lines. PV-10/PH-10 development partnerships and OTC disinvestment could also generate positive cash flows in short term.

Melanoma: Where Are All Concerned Melanoma is an aggressive type of skin cancer with significant morbidity and mortality. Over these last years, an increased awareness of this cancer pathology has led to better diligent screening, improved understanding of its tumorigenesis has guided the development of new therapeutic regimens. Melanoma is a highly curable cancer when detected early but often fatal at advanced stages. US Melanoma Statistics Still Alarming Although overall cancer incidence has annually declined in the US, melanoma incidence has constantly increased over the past decades. In 1975, the incidence of melanoma was 7.9 per 100,000 people. In 2011, the incidence increased to 22.7 per 100,000 people (+187%). The number of new diagnosed melanoma cases in US is estimated by SEER to 76,100 in 2014. Melanoma is the 5th most common cancer diagnosed in US people (4.6% of all new cancer cases). Despite more vigilant screening, early detection and prevention efforts, melanoma mortality has not appreciably declined over the last decades (2.1/100,000 in 1975 vs 2.7/100,000 in 2010). On the other hand, five-year survival rates have significantly improved annually since the 1970s moving from 81.8% (1975) to 91.3% (2004-10). Three distinct pathogenic steps have been proposed in melanoma tumor progression: 1/ in an early-stage tumor, the melanoma may be confined to the epidermis and displays only radial (or lateral) growth. 2/ when melanoma progresses, it can develop into micro invasive melanoma, in which microscopic extensions invade the superficial papillary dermis. 3/ more advanced melanomas can progress to the vertical growth phase, which is characterized by invasive growth with discernable involvement deep into the dermis. In this stage of growth, the melanoma has gained the potential to metastasize. Melanoma Etiology and Genetic Mutations The primary melanoma is a malignant neoplasm of neural crest–derived melanocytes, specialized pigmented cells predominately in the basal layer of the epidermis. The normal function of melanocytes is to produce and transfer a dark pigment called melanin to mitotically active keratinocytes, which are also in the epidermis. The transferred melanin is concentrated in the perinuclear space of keratinocytes and protects the nucleus from UV radiation damage.

5-Year Post-Diagnosis: 91.3% Survival

New cases in 2014

76,100

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N2232,670

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N3224,210

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N4136,830

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2014 - US Melanoma Stats (SEER)

Age Correlation

Median Age of Death

69

Highest Death Rate

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The change of melanocytes to tumor cells occurs in both genetically normal and predisposed patients. Although melanoma pathogenesis is complex and not completely understood, it likely involves interactions between environmental factors, accumulation of sequential genetic alterations, activation of oncogenes, inactivation of tumor suppressor genes, and impaired DNA repair. Many different genes have been associated with increased risk for melanoma. Well characterized mutations involve the highly penetrant gene products of familial melanoma syndromes: p16 (CDKN2A/INK4A), alternate reading frame (ARF) and cyclin-dependent kinase 4 (CDK4). The MC1 receptor gene has also been associated with increased melanoma risk. In addition, a BRAF mutation has been ascertained in up to 60% of cutaneous melanomas. The p16/ARF locus is the best-characterized high-penetrance melanoma gene locus. This locus encodes 2 tumor suppressor proteins that are essential in the pathways of cell growth regulation and apoptosis. Melanoma Risk Factors

Numerous risk factors for melanoma are well documented: natural (frequency of sunburns) and artificial UV (indoor tanning) radiation exposure, family and personal history (high-risk profile in familial melanoma/carriers of mutations), nevi (number of nevi correlated with UV exposure), age, redhead phenotype, white people (inversely correlated to skin pigmentation), induced by UVA therapy (xeroderma pigmentosum, psoriasis). Melanoma Prognosis For thin melanoma lesion, prognosis is usually good. Stage I melanoma has a 5-year survival of 91-95% and 10-year survival of 83-88%. Stage II survival declines to 45-79% (5y) and 32-64% (10y). With advanced stages, the prognosis is poor: Stage III (30-70%, 5y), Stage IV (10-20%, 5y). Palliative radiation therapy can extend to circa 6 months survival of Stage IV patients. Metastatic melanoma has a median survival time of 6-9 months and metastasizes to other skin regions, soft tissues, lung, liver and brain witch is the most common site of Stage IV metastasis with the poorer prognosis. A retrospective review of 6953 patients* indicated a median survival time of 3-4 months with brain metastases and a death rate of 94.5% in the group. (2009 AJCC staging classification) *: Sampson JH, Carter JH Jr, Friedman AH, et al. Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. (J Neurosurg 1998; 88(1):11–20)

Melanoma Treatment: Advances but still Major Unmet Needs The surgical resection is the cornerstone of melanoma treatment. A wide excision is generally recommended with margin (US NCCN guidelines recommend margins up to 2 cm). The sentinel lymph node biopsy is important in melanoma staging, and results from sentinel lymph node biopsy confers important prognostic information. For patients with stage I and II melanoma, surgical therapy would entail wide excision with/without sentinel lymph node dissection. For patients with stage III melanoma with nodal involvement, therapy would involve radical lymphadenectomy. For patients with resectable stage IV, metastasectomy for limited burden disease would be the usual treatment of choice. Until recently, adjuvant systemic therapies have limited success in the treatment of advanced-stage melanoma. Interferon-alpha, an adjuvant treatment approved by FDA for stage III melanoma has shown a limited efficacy with only a 3% increase in 5-year survival (NCI meta-analysis studies). Over these last 5 years, the advent of targeted therapy for BRAF mutated melanoma and immune checkpoint inhibitors, e.g. anti-CTLA-4, anti-PD-1, and anti-PD-1 L antibodies have sparked resurgence of hope for an advanced stage melanoma treatment.

PV-10: Chemoablation - Intralesional Therapeutic Approach. Proposed Mechanism of Action. Provectus Biopharmaceuticals (PVCT)

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LTX-315: Intralesional Therapeutic Approach. Induction of tumor specific immune response. Lytix Biopharma

CAVATAK™: Intralesional Therapeutic Approach with an oncolytic immunotherapeutic agent coxsackievirus A21. Viralytics (VLA)


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793035/

http://www.ncbi.nlm.nih.gov/pubmed/9420067


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Moles: Regular self-exam and annual dermatologic consultation are preventive steps for early melanoma diagnosis. MelaSciences (MELA)

Other investigational research programs in melanoma treatment have positively demonstrated that all therapeutic approaches - even if biological mechanisms are not yet fully documented - need to be explored to support substantial progress in cancer cure with a better quality of life for patients, particularly in advanced stages with poor prognosis. Clinical results of intralesional approaches** - e.g. with small molecule (PV-10 - Provectus Biopharmaceuticals, PVCT), peptide (LTX-315 - Lytix Biopharma), oncolytic immunotherapeutic agents herpes simplex virus (T-VEC™, Talimogene laherparepvec - Amgen) or coxsackievirus A21 (CAVATAK™ - Viralytics, VLA) - make these neoadjuvant therapies significant ways to consider: 1/ in reducing systemic exposure and severe AEs, 2/ increasing agent concentration, 3/ acting possibly as autologous vaccine to induce a systemic immune response and anti-tumor activity (“bystander” effects). ** Plasmid/lipid complex Allovectin® (velimogene aliplasmid, Vical) Phase 3 trial: Aug. 12, 2013 PR - the trial failed to demonstrate a statistically significant improvement in the primary endpoint of ORR (CR and PR after 24 weeks 4.6% vs 12.3% control arm) and secondary endpoint of OS (MOS 18.6 mths vs 24.1 mths control arm). First intralesional therapeutic approach for metastatic melanoma is born in the 1960s with inoculations of Bacille Calmette-Guerin (BCG). Over a 7-year period, 151 patients have been treated with BCG immunotherapy* alone or as adjuvant to surgery. A case was reported for a 77-year old male patient with 64 intracutaneous metastases and a pulmonary metastatic deposit. After an 8-month period of BCG treatment, all the treated lesions were resolved (17/17) with a 50% regression of the pulmonary metastasis. But severe anaphylactic AEs with death were reported in the trial du to BCG systemic dissemination and others randomized trials have failed to confirm any significant clinical benefit. * (D. L. Morton, Ann Surg. Oct 1974; 180(4): 635–641).

Since BCG trials, other intralesional approaches have been conducted in combination with various treatment methods: cryotherapy, electroporation/ECT, carbon dioxide laser and cytokines (IL-2, IFN-alpha, beta).

What’s new in Clinical Trials for Melanoma Therapy?

Viralytics (ASX: VLA) (Abstract #3031)(Updated data PR June 3) VLA updated on ongoing CALM single-arm Phase 2 trial (initiated in 2011) in patients with Stage IIIc and IV malignant melanoma. 54/57 evaluable patients with treated or untreated unresectable Stage IIIC-IVM1c melanoma received 10 intralesional injections of CAVATAK™, Coxsackievirus Type A21, an oncolytic immunotherapeutic agent, into multiple tumors over 18 weeks. Primary endpoint was achieved with 19/51 (37%) evaluable patients displaying irPFS at 6 months. 62% (13/21) of patients surviving 1-year from the initial treatment. Preliminary overall response rate (by irRECIST) is 26% (15/57) of patients. Most common AEs reported were Grade 1 fatigue, chills, fever and local injection site reactions. Estimated final survival data Q1 2015. An extension trial is currently ongoing to extend dosing to 48 weeks (NCT01636882).

Initiation in H2 2014 and completion Q4 2016/Q1 2017. A STORM Phase 1/2 trial started to enrol first patients in March to investigate Intravenous CAVATAK™ Alone and in combo with cytotoxic chemotherapy (e.g. docetaxel) to treat late stage solid tumors (NSCLC, Castrate-resistant Prostate Cancer, Melanoma, Bladder Cancer).(NCT02043665). Preliminary results expected in Q1 2015 and primary completion in Q4 2016.

Melanoma: Female, 70 years. Irregular pigmented skin lesion, dorsum of foot. Melanocyte Pathology website


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1344159/pdf/annsurg00296-0269.pdf


http://www.asx.com.au/asxpdf/20140603/pdf/42q00wdjqr59zv.pdf

http://clinicaltrials.gov/ct2/show/NCT01636882?term=NCT01636882&rank=1

http://clinicaltrials.gov/ct2/show/NCT02043665?term=NCT02043665&rank=1


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Lytix Biopharma (Abstract #3067)(Poster #3067) Update on an open-label, muti-center, dose-escalation Phase 1 trial of LTX-315, a lytic chemically modified 9-mer peptide, by intralesional injection in transdermally accessible tumors. Patients received weekly ultrasound guided injections of LTX-315 into a single tumor for a max. 6 injections. Cohorts 1 and 2 received 10% of the tumor volume until DLT or ≥ 50% necrosis of target tumor was observed. In cohort 3, a fixed dose of 4 mg was injected. Primary endpoint was safety profile and recommended dose. Enrolment included 14 patients with lymphomas (4 patients), malignant melanomas (9 patients) or breast cancer (1 patient). A 65% reduction of tumor volume was observed in one ocular melanoma patient. The intralesional administration of LTX-315 induces cellular lysis (necrosis), leading to release of intracellular content consisting of danger signals such as ATP and HMGB1, together with tumor antigens. Tumour infiltrating lymphocytes and tumour regression were observed in some patients. Results confirm a potential benefit of LTX-315 as a novel intralesional immunotherapy.

A dose escalation, multicenter Phase 1/2a trial is ongoing in Europe (NCT01986426) to evaluate safety, PK and efficacy of different dosing regimens - cohort 1: 2 mg twice per day (4 mg), cohort 2: 3 mg twice per day (6 mg), cohort 3: 4 mg twice per day (8 mg) - of LTX-315 in transdermally accessible tumors including melanoma. Enrolment targets 80 patients and primary completion expected in Dec. 2015.

Amgen (AMGN) AMGN (Abstract #9008a) presented final Overall Survival (OS) data of OPTiM, a randomized Phase 3 trial in unresected stage IIIB/C and IV Metastatic Melanoma, evaluating talimogene laherparepvec (T-VEC) versus subcutaneous (SC) GM-CSF. 436 patients were enrolled: 295 (T-VEC), 141 GM-CSF. Results show a 4.4 month improvement in OS with T-VEC versus GM-CSF (23.3 vs 18.9 months). Objective Response Rate (ORR) with T-VEC was 26% with 11% Complete Response (CR) and 2% for GM-CSF with 1% CR and respectively 16% and 2% for the Durable Response Rate (DRR). Most common adverse events (AEs) with T-VEC were fatigue (50%), chills (49%), and pyrexia (43%). Grade ¾ AEs occurred in +5 patients in either arm (T-VEC arm: Cellulitis 2%). Improvement in OS approaching statistical significance was seen in the Intent-to-Treat (ITT) population. (Abstract # 9029^) Primary data of a multicenter Phase 1b trial to evaluating safety and efficacy of talimogene laherparepvec (T-VEC) and YERVOY® ipilimumab (IPI) with previously untreated, unresected stage IIIB-IV melanoma patients. Of 19 patients enrolled, 18 received T-VEC+IPI. Grade ¾ AEs reported in 32%. Of 17 patients with investigator assessed response, ORR was 41% (24% CR, 18% PR); 35% had SD. Median time to response was 2.9 months. Data reported at the ASCO 2014 Investor Call were better than abstract figures: ORR was improved to 56% (10 patients) from 41% and CR to 33% (6 patients) from 24%. PR was improved to 22% (4 patients) from 18%. A randomized Phase 2 (IPI vs T-VEC+IPI) is ongoing and AMGN will start another Phase 2 trial for a combo T-VEC/pembrolizumab therapy this year and is currently preparing regulatory filing for monotherapy T-VEC in metastatic melanoma.



http://www.lytixbiopharma.com/uploads/Lytix%20Biopharma_poster_ASCO%202014.pdf

http://clinicaltrials.gov/show/NCT01986426




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Debiopharm, Ascenta Therapeutics (Abstract #2532) Data reported on an ongoing open label, multi-center, dose escalation Phase 1 of Debio 1143/AT-406, an oral XIAP inhibitor, in patients with advanced solid tumors and lymphomas. Debio 1143 was given orally once daily on days 1-5 every 2 or 3 weeks. 31 patients received doses from 5 to 900 mg. Estimated enrolment: 50 patients. An antitumor response for one metastatic melanoma patient (11% reduction in target lesion size). Most common AEs were fatigue, nausea and vomiting.

Regeneron (REGN) A poster (Abstract #TPS9120) of a randomized Phase 2 trial of ziv-aflibercept, ZALTRAP® (REGN), and high-dose interleukin-2 (HD IL-2) or HD IL-2 alone for inoperable stage III or IV melanoma. Estimated enrolment is 105 patients with a primary completion in Dec. 2014. A previous Phase 2 trial of ZALTRAP® alone for advanced melanoma showed median OS of 16.3 months and PFS 3.7 months. NewLink Genetics (NLNK) NLMK updated (Abstract #TPS9117) on a Phase 1/2 trial of IDO Pathway inhibitor, indoximod dose escalation in combination with YERVOY® ipilimumab (3mg/kg Q3W x 4 doses) in a standard 3+3 design during the Phase 1 segment. Up to 12 eligible patients with unresectable Stage III or IV melanoma will be enrolled in the Phase 1 portion. The Phase 2 segment will enroll up to 80 patients in a non-randomized trial. IDO pathway inhibitors are another class of immune check point inhibitors akin to the recently developed antibodies targeting CTLA-4 and PD-1. Another randomized Phase 2B trial in Stage 4 metastatic melanoma (Abstract #TPS9115) will enrolled 100 patients receiving either YERVOY® ipilumimab (3mg/kg Q3W x 4) or YERVOY® ipilumimab plus dorgenmeltucel-L 300 million cells per each immunization (HyperAcute® immunotherapy), given weekly x 4, then biweekly for 5 months, monthly for 6 months, and every 3 months for an additional year. Primary endpoint will be the overall clinical response rate and secondary endpoints include DFS, PFS, OS, Duration of CR, Duration of SD and immunologic correlates. A previous Phase 2 trial (The Ochsner Journal, Vol14, N2, 2014) evaluated dorgenmeltucel-L (HyperAcute® immunotherapy) in combination with pegylated interferon-alpha 2b in patients with advanced metastatic, progressive, refractory or recurrent melanoma. 25 patients were enrolled and 21 completed the trial. Results showed that of the 16 patients with stage IV melanoma, 2 had a complete response (CR) per RESIST, one had stable disease (SD), and 4 had no evidence of disease (NED) after resection. Of the 9 patients with stage II/III disease, 3 remained NED, and one stage IIC patient had slow progressive disease (PD) with a single site resected (patient is currently NED). The median overall survival was 29 months, with 60% of the patients surviving for longer than one year. On May 30, of the 25 patients enrolled, 12 (48%) were still alive.

Philogen An ongoing Phase 2 (Abstract #TPS9103^), uncontrolled, multicenter, prospective trial will enroll up to 20 patients (15 enrolled so far) with unresectable Stage IIIC/IVM1a melanoma. Cutaneous or subcutaneous injectable metastases will receive intratumoral injections of darleukin (L19-IL2) (10 Mio IU max. daily dose) in combination with Fibronum (L19TNFalpha) (312 µg) once per week for 4 consecutive weeks.






http://investors.linkp.com/common/download/download.cfm?companyid=AMDA-NRWRB&fileid=758644&filekey=5f093ecb-6838-4558-b923-23972a2649ae&filename=Link_08-ochs-14-02-32_164_174_tkw.pdf



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Primary endpoint is CR rate of L19IL2/L19TNF-treated lesions at week 12. Secondary endpoints include ORR and DCR of treated lesions at week 12, and ORR and disease control rate (DCR) at weeks 12, 24 and 36 of treated/non-treated lesions. Updated results of a Phase 2 (Abstract #9041^) trial of 25 patients (24 evaluated) with unresectable Stage IIIB/IIIC melanoma. Cutaneous/subcutaneous injectable metastases received intratumoral injections of darleukin (L19-IL2) once per week at a maximum daily dose of 10 MIU for 4 consecutive weeks. Tumor response was evaluated 12 weeks after the first treatment. A complete response of all metastases was achieved in 6 patients (25%), which was long-lasting in most cases (5 patients +24 months). Toxicities were mild and comparable to that of free IL2. No serious AE was recorded. Novartis (NOVN), GlaxoSmithKline (GSK) (Abstract #9011^) Data were reported on COMBI-d trial, a randomized, double-blinded Phase 3 comparing TAFINLAR® dabrafenib (D) / MEKINIST® trametinib (T) combination, trametinib to dabrafenib and trametinib to placebo (P) as first-line therapy in patients with unresectable or metastatic BRAFV600E/K mutation-positive cutaneous melanoma. 423 patients were randomized 1:1 (until Jan. 2013) to receive D (150 mg twice daily) + T (2 mg once daily) or D + placebo (P). Median follow-up was 9 months. Data show the combination D+T was associated with only a modest improvement in PFS (9.3 months vs 8.8 months with D+P; HR 0.75), consistent with the Phase 1/2 data. ORR was 67% vs 51%. HR for interim OS was 0.63 for D+T. AEs rates were similar for both arms. Increased incidence (51%) and severity (grade 3, 6%) of pyrexia occurred with D+T vs D+P. PFS for TAFINLAR® mono-therapy arm was reported to be greater in the Phase 3 trial than in prior Phase 1/2 trial (8.8 months/COMBI-d vs 5.8 months/Phase 1/2); this resulting in a more modest treatment benefit of 0.5 months from combo-therapy, relative to 3.6 months benefit from the Phase I/II trial. OS COMBI-d data readout is expected for Q4’14/Q1’15. GSK updated OS data (Abstract #9010^) of Phase 1/2 trial evaluating TAFINLAR® dabrafenib (D) vs D+T combo in patients with BRAFV600 mutation-positive metastatic melanoma. With median follow-up of 28 (part B/Ph1, 77 patients BRAF naive) and 24 months (part C/Ph2: 162 patients), OS in part C was 23.8 months (HR=0.73 vs D mono) for D (150mg BID) + T (2mg QD). 18-month OS rate was 63%. Novartis acquired these assets as part of the recently announced three-part transaction with GSK including a marketed oncology portfolio for a total cash consideration of $16.0bn (up to $1.5bn of consideration depending on the results of this COMBI-d trial).

AstraZeneca (AZN) (Abstract #3001^) Data from the dose-escalating Phase I trial of PD-L1 MEDI4736 includes data on 26 patients (13 NSCLC, 8 melanoma, 5 other), with partial responses in 4 patients (3 NSCLC, 1 melanoma) and 5 additional pts with tumor shrinkage not meeting PR. ORR = 15% and disease control rate (PR + SD ≥ 12 wks) = 46%. Compares to ORR’s of 13-41% reported from other trials but numbers are too small for conclusions. Data from the expansion cohort are only preliminary including safety data on 105 patients (targeting up to 600 patients) in the abstract (Abstract #3002^) with no concerning signals (1 grade 2 pneumonitis). Treatment-related AEs occurred in 33% with related + Grade 3 AEs in 7%. The most frequently observed treatment-related AEs were fatigue (13%), nausea (8%), rash (6%), vomiting (5%), and pyrexia (5%). With a median follow-up of 6 weeks, tumor shrinkage is already detectable in multiple tumor types including pts with melanoma, pancreatic, head and neck, and gastroesophageal cancer. CANOPY & CO. LTD DISCOVERY 360° - A CANOPY VIEW PAGE 9







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Data from a trial of EGFR inhibitor AZD9291 show solid responses in EGFR T790M+ pts (64%) with lower efficacy in T790M negative patients (23%). No dose limiting toxicities were observed. Although AstraZeneca has stated the drug was “well tolerated”, the investigators highlight 5 reports of an interstitial lung disease-like events that are under investigation and could be concerning. Celldex Therapeutics (CLDX) (Abstract #3027) Updated Phase 1 data provided for solid tumors arm (3mg/kg weekly) on the expansion cohorts of melanoma (n=16) and RCC patients for CLDX’s varililumab (CDX-1127), an anti-CD27 agonist antibody (activation pathway of lymphocytes). The median number of prior therapies is one anti-cancer for metastatic melanoma. 13/16 patients in the metastatic melanoma arm had checkpoint blockade prior to entering the varililumab study; the remaining three refused or were determined by their physician to be ineligible for checkpoint blockade. 3/14 evaluable melanoma patients have ongoing stable disease (SD) with a PFS range of 2.7+ to 11.5+ months, including a uveal melanoma patient with 12% shrinkage of measurable disease. Dose-escalation completed at 10 mg/kg with one dose-limiting toxicity, grade 3 transient asymptomatic hyponatremia, at 1.0 mg/kg. AEs were generally grades ½ included fatigue, rash, nausea, decreased appetite and headache. Varililumab is well tolerated and induces immune activation consistent with CD27 co-stimulation. In 2H14, CLDX plans to initiate: 1/ a Phase 1/2 simultaneous combination trial of varililumab with nivolumab in patients with melanoma, non-small cell lung cancer, colorectal, head and neck and ovarian cancers. Enrolment target is 170 patients; 2/ a Phase 1/2 trial of simultaneous varililumab and YERVOY® in first- or second-line therapy for advanced melanoma with up to 72 patients enrolled in Phase 2 portion. The trial will include up to 24 patients with NY-ESO+ metastatic melanoma; 3/ a Phase 1/2 trial of varililumab plus the BRAF pathway targeted agents, dabrafenib and trametinib (followed sequentially by a checkpoint inhibitor) for patients with BRAF mutated metastatic melanoma.

Incyte (INCY) (Abstract #3010) INCY reported on preliminary results for an ongoing open-label, dose escalation Phase 1/2 trial of INCB24360, an oral IDO1 inhibitor, combined with YERVOY® ipilimumab (IPI) (3 mg/kg IV Q3W x 4) in unresectable or metastatic melanoma patients. Endpoints included safety and tolerability, OR (by irRC and RECIST, every 9 weeks), DR, OS, PFS, and IDO1 inhibition. The trial was initiated in 2012. Enrolment in 2 cohorts (300 mg BID/7 patients, 25 mg BID/8 patients) is completed. Results show that 42% (5/12) of immunotherapy-naive patients who received IPI with INCB24360 at 25 mg or 50 mg twice-daily demonstrated an OR (complete response + partial response) and 75% (9/12) achieved DC (complete response + partial response + stable disease) as assessed using irRC. 6/8 patients had tumor reduction by the 1st evaluation. One patient with pulmonary metastases treated with IPI plus INCB24360 50 mg twice-daily experienced a CR. Immune-related AEs in the cohorts were generally grades ½. Grades ¾ immune related AEs were qualitatively similar to IPI monotherapy. A 50 mg BID cohort is enrolling. Indoleamine 2, 3-dioxygenase (IDO), is an immune regulatory enzyme that is normally expressed in tumor cells and in activated immune cells.





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Neostem (NBS)

(Abstract #3090) NBS reported pooled data analysis from 170 melanoma patients for 3 trials conducted from 1990-2011: a single-arm Phase 2 trial of irradiated, proliferating, autologous tumor cells, a single-arm Phase 2 trial of melapuldencel-T, and a randomized trial directly comparing the 2 therapies. 27 comparator-treated patients were excluded to decrease interpatient differences associated with poor survival.

Remaining patients were classified as NED (no evidence of disease) or non-NED. 5Y OS for all 73 non-NED was 27% (median 25.5 months). 15/23 survivors had been followed for at least 5 years. 5Y OS was better in melapuldencel-T cohort (33%) vs comparator cohort (20%). In the subset of patients (32) who had measurable disease by RECIST, 5Y OS was 20% for melapuldencel-T vs 10% for comparator.

In the previous Phase 2, the 2Y OS was 72% for melapuldencel-T therapy group vs 31% for control group (irradiated tumor cells only) with no serious AEs related to immunotherapy and minor local injection site reactions.

Last December, California Stem Cell (CSC), an NBS’s subsidiary, received an FDA agreement for its INTUS Phase 3 initiation trial application to explore the potential of

DC-TC, melapuldencel-T, a cancer stem cell-based therapy, to treat advanced metastatic melanoma. The protocol has received Special Protocol Assessment (SPA) and DC-TC received a Fast Track Designation. FTD designation is given to therapies which show promise in treating life-threatening medical conditions, which accelerates the approval of investigational new drugs undergoing clinical trials. This US-EUR multi-center, randomized, double-blind trial will compare overall survival (OS) of patients receiving CSC’s patient-specific cancer immunotherapy DC-TC, melapuldencel-T (autologous dendritic cells pulsed with irradiated tumor cells in GM-CSF - weekly injections for 3 consecutive weeks and then once monthly for 5 months), against patients receiving a control therapy (autologous mononuclear cells in GM-CSF). The enrolment will target up to 250 patients with recurrent Stage III/Stage IV metastatic melanoma. The Phase 3 enrolment is expected to start by the end of 2014.

DC-TC therapy approach: it starts with cancer stem cells (SC) that have been isolated from a patient’s resected tumor sample, enriched and inactivated. The newly created cancer SC line is combined with dendritic cells or antigen-presenting immune cells that are derived from the same patient’s blood. The product is then injected back (subcutaneous) into the patient.

Celgene (CELG)

Final overall survival (OS) was presented by CELG (Abstract #9045) for a Phase 3 trial of ABRAXANE®, nab-paclitaxel versus dacarbazine (DTIC) in chemotherapy-naive patients with metastatic melanoma. 529 patients with chemotherapy-naive, stage IV melanoma were enrolled. With a median follow-up of 30 months (data cut off on Sept. 2013), 427 patients died: 81% (215) in the nab-paclitaxel arm versus 80% (212) in the DTIC arm; Median OS for nab-paclitaxel did not reach statistical significance vs DTIC (12.6 vs 10.5 months). The use of post study anticancer therapy did not differ by treatment arm (77% nab-paclitaxel vs 73% DTIC). Similar results were also observed with the use of a BRAF inhibitor (13% vs 10%) or ipilimumab (31% vs 32%). Most common AEs reported were peripheral neuropathy and neutropenia. The primary endpoint was met with a significant improvement in PFS (by RECIST): 4.8 months for nab-paclitaxel vs 2.5 months for DTIC (median data).





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Roche (ROG) (Abstract #TPS9118^) Update on ongoing BRIM8, a randomized, double-blind, placebo-controlled Phase 3 trial evaluating ZELBORAF®, vermurafenib, a BRAF kinase inhibitor as adjuvant therapy in patients with surgically resected, stage IIC or III BRAFV600 mutation+ cutaneous melanoma. Two cohorts will enroll approx. 725 patients: C1/ 500 patients with completely resected stage IIC, IIIA, or IIIB cutaneous melanoma; C2/ 225 patients with stage IIIC cutaneous melanoma. Patients will be randomized 1:1 to receive vermurafenib (960 mg bid) or placebo for 52 weeks with randomization stratified by pathologic stage and region (C1) and by region (C2). Primary endpoint is disease-free survival and secondary endpoints include OS and distant metastasis-free survival. As of Jan. 2014, 154 patients have been enrolled. Estimated trial completion: March 2022 and final data collection for primary endpoint in June 2016. Novartis (NOVN), Array BioPharma (ARRY) Binimetinib, a selective MEK inhibitor, was licensed by Array Biopharma to Novartis in 2010. NOVN (Abstract #TPS9102) presented MEMO, an ongoing Phase 3 randomized, open-label trial of binimetinib (MEK162) versus dacarbazine designed for an enrolment of 393 patients. Included patients have advanced unresectable or metastatic cutaneous melanoma with NRAS Q61 mutation previously untreated or has progressed after 1 line of immunotherapy. NRAS-mutant melanoma is the first potential indication for binimetinib. Primary endpoint is Progression-Free Survival (PFS) and regulatory filing, supported by these Phase 3 trial data, is expected in 2015. NOVN also presented early data (Abstract #9009) of a Phase 1b/2 study of LEE011, a CDK4/6 inhibitor, in combination with binimetinib (MEK162) in patients with NRAS-mutant melanoma. Updated to March, 22 patients were enrolled. Interim results (21 evaluable patients) show a partial response for 33% (7 with 3 confirmed) and a stable disease for 52% (11). Several patients experienced early tumor shrinkage with major symptomatic improvement. 12 patients remain on treatment (55%, duration 2 to 8 months). Most common AEs included CPK and creatinine elevation, rash, edema, anemia, nausea, diarrhea and fatigue. A third poster (Abstract #9051) was presented on a phase 1b dose-escalation trial of BYL719 (NOVN), a PI3K inhibitor, in combination with binimetinib (MEK162) in patients with selected advanced with RAS- and BRAF-mutant solid tumors (over 10 tumor types). A partial response (PR) was observed in one patient with NRAS-mutant melanoma (confirmed). ARRY expressed interest in getting back rights from NOVN on binimetinib. On last FY3Q14 conference call, ARRY noted NVS has confirmed a first binimetinib regulatory filings for MEMO/NRAS-mutant melanoma in 2015 and for COLUMBUS/BRAF-mutant melanoma in 2016.







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Immune Checkpoint Modulators – PD-L1 in Melanoma Antibodies directed against Programmed Death 1 (PD-1) and its ligand PD-L1 have shown much promise in melanoma, renal cell cancer, NSCL cancer and other solid tumors with encouraging rates and durability of tumor responses. Merck (MRK) Pembrolizumab (MK-3475) efficacy and safety was evaluated in 411 melanoma patients (Abstract #LBA9000^) with a nonrandomized cohort of YERVOY® ipilimunab-naive (IPI-N) and IPI-treated (IPI-T) plus MK-3475 regimens and randomized cohorts of IPI-N and IPI-T plus MK-3475 regimens. As of Oct. 2013 cut off, all patients had +6 months follow-up and 75% +9 months. Among 365 patients with measurable disease at baseline, ORR (by RECIT) was 40% in IPI-N and 28% in IPI-T. Median PFS (by RECIT) was 24 weeks in IPI-N and 23 weeks in IPI-T. Responses were durable (88% ongoing at analysis). Median OS was not reached, with 1Y OS of 71% in all patients. 12% of patients experienced grade ¾ AEs and 4% discontinued trial due to drug-related AEs. Update on Phase 1 of pembrolizumab (MK-3475) (Abstract #3005^) with 135 patients melanoma receiving 10 mg/kg Q2W (n = 57), 10 mg/kg Q3W (n = 56), or 2 mg/kg Q3W (n = 22). At cut off, Oct. 2013, all patients had +13 months follow-up, with a median time on treatment of 23 weeks. ORR was 41% (by RECIST). Objective responses were observed as late as week 64 with some conversion to control rate (DCR) as late as week 72. Median response duration (DR) was not reached with 87% of responses ongoing at cut off date. Median PFS was 31 weeks and 1Y OS 81%. Tumor PD-L1 expression was evaluable in 71 patients with measurable disease and ≥1 tumor evaluation (77% PD-L1+). PD-L1 expression was associated with improved ORR by RECIST (51% vs 6%) and PFS (12 vs 3 months), 1Y OS 84% in PD-L1+ (vs 69% PD-L1–). No treatment-related deaths; 14% of patients experienced drug-related grade ¾ AEs. Updated results on ongoing randomized trial of pembrolizumab (MK-3475) (Abstract #3000) with 276 melanoma patients in cohorts YERVOY® ipilimunab-naive IPI-N (103) and IPI-R (173) receiving 2mg Q3W or 10mg Q3W. YERVOY® naive patients could have received up to 2 prior systemic therapies and YERVOY® experienced cohort had no limit for prior treatment. All BRAF-mutant patients were previously treated with a BRAF inhibitor. Using the immune-related response criteria (irRC) assessment, similar response was observed for the 2 doses. No significant differences in ORR by RECIST were observed between doses in IPI-N (33% vs 40%) and IPI-R (ident. 26%) patients. Median response duration (DR) was not reached (range from +6 weeks to +39 weeks), with 90% of responses ongoing. Median PFS ranged from 14 to 35 weeks across the cohorts. No treatment-related deaths; safety profile was generally similar between 2mg Q3W and 10mg Q3W patients. Another abstract (Abstract #3006^) discussed the assessment of the immune-related response criteria (irRC) combining data from these 2 previous trials. Among the 411 patients enrolled across the 3 cohorts, 192 were on MK-3475 for +28 weeks (cut-off of Oct. 2013). Tumor flare observed in 3.6% of patients and atypical delayed response in 3.1%. Comparing the responses with RECIST or irRC, for 215 patients with CR/PR/SD by RECIST and irRC, OS at 12 months reached 92% versus 67% for 61 patients with PD by RECIST and CR/PR/SD by irRC, 34% for 145 patients with PD by RECIST and irRC. Authors concluded to an underestimation of benefit for MK-3475 in approx. 10% of patients with conventional criteria as RECIST. Waiting for updated data.








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BMS (BMY), Ono Pharmaceutical (4528) Updated results on nivolumab (BMS-936558, ONO-4538), IgG4 anti-PD-1, Phase 1 trial (Abstract #9002). Previously treated advanced melanoma patients with no prior YERVOY® ipilimumab therapy received nivolumab doses (0.1-10 mg/kg IV) Q2W for up to 96 weeks. They were evaluated for OS and PFS. On 107 melanoma patients who initiated therapy with nivolumab from 2008-2012, 25% had +3 prior therapies. OS rates (years 1-3) were respectively 63%, 48% and 41%. For 32% of patients with OR, median response duration (DR) was 22.9 months. 24 OR patients stopped nivolumab (not disease progression-related), 46% of patients maintained responses for over 24 weeks off drug (24-56 weeks range), 4% of patients had unconventional immune-related responses. In a subset of 41 patients with evaluable tumor for PD-L1+/- expression analysis, had median OS not reached vs 12.5 months and PFS was 9.1 vs 1.9 months. Ongoing Phase 3 trials are evaluating PD-L1 as a potential predictive biomarker for response to nivolumab. (Abstract #3009) Update on a pilot, open-label, single center, multi-dose, dose-escalation Phase 1 trial of nivolumab in combination with/without a peptide vaccine: regimens were administered to 105 patients with unresectable melanoma that failed at least one regimen and were IPI-N or progressed after IPI. Median follow-up for all patients was 15 months; median PFS was 4.2 months, and estimated median OS was 16.7 months with 1Y OS of 65%. Median OS was similar for YERVOY® IPI-naïve (15.9 months) or YERVOY® IPI-relapsed patients (18 months). Biomarker studies showed that circulating HLA-DR lo/CD14+/CD11b+ myeloid-derived suppressor cells, and FCRL2+ CD8 T cells were associated with progression. Decreased regulatory molecules BTLA and LAG3 on CD8+ T cells were associated with response. Survival and clinical data were reported on a Phase 1 trial of concurrent and sequenced nivolumab, YERVOY® (NIVO) plus ipilimumab (IPI) (Abstract #LBA9003^) in advanced melanoma. 53 patients were enrolled in 2009-12. 1Y and 2Y Overall Survival were respectively 82% and 75%. Concurrent NIVO + IPI therapy showed encouraging survival and manageable safety profile. Median OS was respectively 39.7 and 13 months for concurrent (53 patients) and sequenced (32 patients) regimens.

CureTech Results of a Phase 2 multicenter, randomized, open-label, study to evaluate the safety and efficacy of CuraTech’s pidilizumab (CT-011), a humanized anti PD-1 IgG1k, in metastatic melanoma patients (Abstract #9001). Patients were randomized to 2 dose levels (1.5 or 6 mg/kg IV Q2W). On the 103 enrolled patients, 75% with M1c melanoma stage, 15.5% with brain metastases, 30% with elevated LDH, 33% with disease spread to +3 organs. 77% received prior systemic therapy for melanoma: 51% prior YERVOY® IPI, 7.8% prior BRAF inhibitor, 44% prior cytokines. 45% did not respond to most recent therapy. 45% received pidilizumab less than 4 months after prior therapy. ORR using irRC for all patients was 5.9% and 10% in the 1.5mg/kg prior YERVOY® IPI cohort. Patients with prior YERVOY® IPI had higher irSD (53.7% vs 20.5%) and slightly longer median PFS (2.8 vs 1.9 months). OS at 12 months was 64.5% without significant differences between baseline data or prior therapy. Most frequent AEs were fatigue, diarrhea, arthralgia and pneumonia (5%) and dyspnea (3%) SAEs were also reported.

See Annex for Melanoma Abstracts and Trial Protocol References pages 18-22.







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Melanoma Clinical Trials – Key ASCO 2014 Updates

Phase 1 Phase 2 Phase 3 Registration

Talimogne laherparepvec - T-VEC (AMGN)

Debio 1143/AT-406 (Debiopharm/Ascenta Therapeutics)

Ziv-aflibercept - ZALTRAP (REGN)

Pembrolizumab - MK-3475 (MRK)

Nivolumab (BMY/Ono Pharmaceutical)

Pidilizulimab - CT-011 (CureTech)

Indoximod (NLNK)

Darleukin - L19-IL2 (Philogen)

Selumetinib - ARRY-142886 (AZN/ARRY)

Unresected stage IIIB/C and IV Metastatic Melanoma. Versus GM-CSF

T-VEC+IPI versus IPI

T-VEC + ipilimumab (IPI) with previously untreated, unresected stage IIIB-IV melanoma patients

Advanced solid tumors (including metastatic melanoma) and lymphomas

Ziv-aflibercept + HD IL-2 or HD IL-2 alone for inoperable stage III or IV melanoma

Non rand. Cohort ipilimunab-naive (IPI-N) and IPI-treated (IPI-T) + MK-3475 regimens and randomized cohorts of IPI-N and IPI-T + MK-3475 regimens in melanoma patients

MK-3475 10 mg/kg Q2W, 10 mg/kg Q3W or 2 mg/kg Q3W in melanoma patients

MK-3475 in cohorts YERVOY® ipilimunab-naive IPI-N (103) and IPI-R (173) receiving MK-3475 2mg Q3W or 10mg Q3W

Previously treated advanced melanoma patients with no prior IPI therapy received nivolumab doses (0.1-10 mg/kg IV) Q2W

Nivolumab in combination with/without a peptide vaccine in melanoma patients

Nivolumab + plus ipilimumab in advanced melanoma

Pidilizumab in metastatic melanoma patients (1.5 or 6 mg/kg IV Q2W)

Indoximod dose escalation + ipilimumab (3mg/kg Q3W x 4 doses) in patients with unresectable Stage III or IV melanoma

Ipilimumab (3mg/kg Q3W x 4) or ipilimumab + dorgenmeltucel-L in Stage IV metastatic melanoma patients Dorgenmeltucel-L (NLNK)

Dorgenmeltucel-L + pegylated interferon-alpha was recently completed in patients with stage IIIC or IV metastatic, progressive, refractory, or recurrent melanoma

Phase 1/2 of darleukin + dacarbazine in patients with metastatic melanoma

Phase 2a/b of darleukinL19IL2 + dacarbazine in patients with metastatic melanoma

Intratumoral injection of darleukin in patients with stage III/IV melanoma

Fibromum - L19-TNF (Philogen) Fibronum + melphalan using isolated inferior limb perfusion (ILP) in patients with in-transit stage III/IV melanoma

Dabrafenib - TAFINFLAR (NOVN/GSK) Dabrafenib + trametinib, trametinib to dabrafenib and trametinib to placebo as first-line therapy in patients with unresectable or metastatic BRAFV600E/K mutation-positive cutaneous melanoma

Phase 1/2 for dabrafenib vs dabrafenib + trametinib in patients with BRAFV600 mutation-positive metastatic melanoma

MEDI4736 (AZN) MEDI4736 in advanced solid tumors including ocular and cutaneous melanoma patients

Selumetinib + dacarbazine compared with placebo + dacarbazine as first systemic therapy in metastatic uveal melanoma (SUMIT)

Varililumab - CDX-1127 (CLDX) Varililumab (3mg/kg weekly) - expansion cohort in solid tumors including metastatic melanoma patients

INCB24360 (INCY) Phase 1/2 with INCB24360 + ipilimumab (3 mg/kg IV Q3W x 4) in unresectable or metastatic melanoma patients

Melapuldencel-T (NBS) Melapuldencel-T in recurrent Stage III/Stage IV metastatic melanoma. Phase 3 protocol has received Special Protocol Assessment (SPA)

Nab-paclitaxel - ABRAXANE (CELG) Nab-paclitaxel versus dacarbazine (DTIC) in chemotherapy-naive patients with Stage IV metastatic melanoma

Vermurafenib - ZELBORAF (ROG) Vermurafenib as adjuvant therapy in patients with surgically resected, stage IIC or III BRAFV600 mutation+ cutaneous melanoma.

Rose Bengal - PV-10 (PVCT) Phase 2: PV-10 in cutaneous and subcutaneous injections with refractory cutaneous melanoma patients

Rose Bengal - PV-10 (PVCT) Phase 1: PV-10 immune and clinical efficacy in patients with injected and uninjected metastatic melanoma lesions

MELANOMA CLINICAL PIPELINE - ASCO 2014 UPDATES

Binimetinib - MEK162 (NOVS/ARRY) MEMO Phase 3: binimetinib (MEK162) versus dacarbazine in parients with advanced unresectable or metastatic cutaneous melanoma with NRAS Q61 mutation

LEE011 (NOVS) Phase 1b/2: LEE011 in combination with binimetinib (MEK162) in patients with NRAS-mutant melanoma

BYL719 (NOVS) Phase 1b: BYL719 in comb. with binimetinib in patients with selected adv. solid tumors (RAS- and BRAF-mutants)

LTX-315 - ONCOPORE (Lytix Biopharma) Phase 1: dose-escalation of TX-315 (5 mg/ml-70 mg/ml) in patients with a transdermally accessible tumor including melanoma

Phase 1/2a: LTX-315 in patients with with transdermally accessible tumors incl. melanoma

Coxsackievirus A21 - CAVATAK (VLA) STORM Phase 1/2 trial: IV CAVATAK™ alone/combo with cytotoxics in late stage solid tumors including Melanoma

Coxsackievirus A21 - CAVATAK (VLA) Extension Phase 2 trial: Efficacy and Safety of Intratumoral coxsackievirus A21 in Patients with Stage IIIc and Stage IV malignant melanoma to extend

Coxsackievirus A21 - CAVATAK (VLA) CALM Phase 2: intralesional injections of coxsackievirus A21 in patients with Stage IIIc and IV malignant melanoma



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Oncology Lexicon

Disease-Free Survival (DFS): period of time after curative therapy when no disease symptoms can be detected. Survival period after a primary curative cancer therapy without any signs or symptoms of that cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new cancer therapy works. Also called Relapse-Free Survival (RFS).

Progression-Free Survival (PFS): period of time during and after cancer therapy when disease remains stable (SD). In a clinical trial, measuring the progression-free survival is another way to see how well a new cancer therapy works. A “progressive disease” is considered one in which the longest diameter of a cancerous lesion has increased at by at least 20%, since treatment has started.

Overall Survival Rate (OSR): percentage of people in a trial or treatment group who are still alive for a certain period of time after they were diagnosed with or started cancer therapy. The overall survival rate is often stated as a 5-Year Survival Rate, which is the percentage of people in a study or treatment group who are alive 5 years after their diagnosis or the start of cancer therapy. 10-Year Survival Rate is also used. Also called Survival Rate.

Complete Response (CR): complete resolution or disappearance of all target lesions/signs of cancer in response to therapy. This does not always mean the cancer has been cured. Also called Complete Remission.

Duration of Response (DR): The cancer lesions coming back again some time after they have disappeared is called relapse or recurrence. When a cancer that has shrunk starts to grow again, it is called progression. The time to relapse or progression is the duration of response. Response duration for an individual patient is given as a number possibly with a plus sign after it like "5+"; “plus” sign means the response is still ongoing at the last evaluation. A lack of sign means the patient relapsed.

Duration of Stable Disease (DSD): Stable disease is measured from the start for therapy (start of randomisation in trials) until the criteria for progression are met.

Duration of Overall Response (DOR): it measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive cancer disease is objectively documented.

Durable Response Rate (DRR): period of time when a partial or complete response is observed, as a result of therapy. Some melanoma treatment trials only show a very weak percentage of patients having a durable response, across all of the patients in a trial group, meaning that melanoma cancer is a problematic disease to cure. A durable response is a good indicator that experimental therapy has a lasting effect and may be viable melanoma treatment, if coinciding with an improvement in Overall Survival (OS).

Melanoma: form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole/melanocytic nevus/pigmented nevus (skin melanoma), but can also begin in other pigmented tissues: eye (Ocular Melanoma, Conjunctival Melanoma), intestines (Small-bowel Melanoma, Colon Melanoma and Anorectal Melanoma). Advanced Melanoma: cancerous cells have spread from the original melanoma to other parts of the body (Metastasis). Most likely to spread to one or more of the following parts of the body: 1/ Skin’s areas distant from the original melanoma, 2/ Lymph nodes distant from the original melanoma, 3/ Lungs, 4/ Liver, 5/ Bones, 6/ Brain.



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Skin Melanoma: 4 types of cutaneous melanoma. 1/ Superficial Spreading Melanoma: the most common type of skin melanoma. In women the most common place for it to start is on the legs; in men it’s on the chest and the back. Usually the melanoma cells grow slowly at first, spreading out across the surface of the skin. 2/ Nodular Melanoma: second most common type. It can grow more quickly than other melanomas and is usually found on the chest, back, head or neck. 3/ Lentigo Maligna Melanoma: usually found in older people in areas of skin that have had a lot of exposure to the sun over many years (most often the face and neck). It develops from a slow-growing precancerous condition called a lentigo maligna or Hutchison’s freckle, which looks like a stain on the skin. 4/ Acral Lentiginous Melanoma: rarest type and is usually found on the palms of the hands, soles of the feet, or under fingernails or toenails. It’s more common in people with black or brown skin and isn’t thought to be related to sun exposure.

Median Overall Survival (MOS): period from either the date of diagnosis or the start of cancer therapy, that 50% of patients in a group of patients diagnosed with the disease are still alive. In a clinical trial, measuring the median overall survival is one another way to see how well a new treatment works. Also called Median Survival (MS).

RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments. The original criteria were published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute (NCI) of the United States and the National Cancer Institute of Canada Clinical Trials Group. RECIST 1.1, published in January 2009, is an update to the original criteria. Today, the majority of clinical trials evaluating cancer treatments for objective response in solid tumors are using RECIST.

Progression Disease (PD): A least a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5 mm.

Stable Disease (SD): cancer that is neither decreasing nor increasing in extent or severity.

Partial Response (PR): decrease in a tumor size, or in extent of cancer in the body (e.g., metastasis), in response to therapy. A partial decrease of at least 30% of the sum of diameters of target cancerous lesions; sometimes also referring to a 30% decrease in the number of lesions. Also called Partial Remission.

Median Duration of Response (MDR): period of time when cancer disease is expected to respond to the therapy before relapse or progression.

Neoadjuvant Therapy: a treatment regimen given as a first step to shrink a tumor before the main therapy, which is usually surgery, is given. Neoadjuvant therapies include chemotherapy, radiation therapy, and hormone therapy.


PROVECTUS BIOPHARMACEUTICALS – NYSE-MKT: PVCT JUNE 11, 2014

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ASCO 2014 – MELANOMA SELECTED ABSTRACTS TRIAL DATA COMPANY FIRST AUTHOR ABSTRACT CALM study: A phase II study of an intratumorally delivered oncolytic immunotherapeutic agent, coxsackievirus A21, in patients with stage IIIc and stage IV malignant melanoma.

NCT01227551 Viralytics Robert Hans Ingemar Andtbacka

3031

Metabolic tumor burden for prediction of overall survival following combined BRAF/MEK inhibition in patients with advanced BRAF mutant melanoma.

NCT01271803 Roche Grant A. McArthur 9006^

BRIM8: A phase III, randomized, double-blind, placebo-controlled study of vemurafenib adjuvant therapy in patients with surgically resected, cutaneous BRAF-mutant melanoma at high risk for recurrence (NCT01667419).

NCT01667419 Roche Karl D. Lewis TPS9118^

NCI 8628: A randomized phase II study of ziv-aflibercept (Z) and high-dose interleukin-2 (HD IL-2) or HD IL-2 alone for inoperable stage III or IV melanoma—Efficacy and biomarker study.

NCT01258855 Regeneron Madeeha Ashraf TPS9120

Efficacy of intralesional Rose Bengal in patients receiving injection of all existing melanoma in phase II study PV-10-MM-02.

NCT00521053 Provectus Biopharmaceuticals

Sanjiv S. Agarwala 9027

Assessment of immune and clinical efficacy after intralesional PV-10 in injected and uninjected metastatic melanoma lesions.

NCT01760499 Provectus Biopharmaceuticals

Amod Sarnaik 9028

Intralesional treatment of stage III metastatic melanoma patients with L19-IL2: Clinical and systemic immunological responses.

NCT01253096 Philogen Dario Neri 9041^

A phase II study of intratumoral application of L19IL2/L19TNF in melanoma patients in clinical stage III or stage IV M1a with presence of injectable cutaneous and/or subcutaneous lesions.

EudraCT 2012-001991-13

Philogen Riccardo Danielli TPS9103^

Phase I/II study of the TLR3 agonist poly-ICLC as an adjuvant for NY-ESO-1 protein vaccination with or without Montanide ISA-51 vg in patients with melanoma.

NCT01079741 Oncovir Rachel Lubong Sabado TPS9119

Systemic antitumor effect and clinical response in a phase 2 trial of intratumoral electroporation of plasmid interleukin-12 in patients with advanced melanoma.

NCT01502293 OncoSec Medical Adil Daud 9025^

A phase 1b/2 study of LEE011 in combination with binimetinib (MEK162) in patients with NRAS-mutant melanoma: Early encouraging clinical activity.

NCT01449058 Novartis Jeffrey Alan Sosman 9009

Phase I dose-escalation study of the protein kinase C (PKC) inhibitor AEB071 in patients with metastatic uveal melanoma. NCT01430416 Novartis Sophie Piperno-Neumann

9030

A phase 1b dose-escalation study of BYL719 plus binimetinib (MEK162) in patients with selected advanced solid tumors.

NCT01449058 Novartis Dejan Juric 9051

A phase I trial of BKM120 combined with vemurafenib in BRAFV600E/k mutant advanced melanoma. NCT01512251 Novartis Alain Patrick Algazi 9101 NEMO: A phase 3 trial of binimetinib (MEK162) versus dacarbazine in patients with untreated or progressed after first-line immunotherapy unresectable or metastatic NRAS-mutant cutaneous melanoma.

NCT01763164 Novartis Keith Flaherty TPS9102

NLG-0304: A phase 2B study of ipilimumab with or without dorgenmeltucel-L (HyperAcute-Melanoma) immunotherapy for patients with stage IV melanoma.

NCT02054520 NewLink Genetics Adam I Riker TPS9115

Phase 1/2 trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus ipilimumab for the treatment of unresectable stage 3 or 4 melanoma.

NCT02073123 NewLink Genetics Eugene Kennedy TPS9117

Long-term survival for patients with detectable metastatic melanoma at time of treatment with patient-specific tumor stem cell vaccines.

Refer to NCT00436930

Neostem-CSC Robert Owen Dillman 3090

Randomized comparison of two doses of the anti-PD-1 monoclonal antibody MK-3475 for ipilimumab-refractory (IPI-R) and IPI-naive (IPI-N) melanoma (MEL).

NCT01295827 MRK Omid Hamid 3000

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ASCO 2014 – MELANOMA SELECTED ABSTRACTS TRIAL DATA COMPANY FIRST AUTHOR ABSTRACT Clinical efficacy and correlation with tumor PD-L1 expression in patients (pts) with melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475.

NCT01295827 MRK Richard Kefford 3005^

Evaluation of immune-related response criteria (irRC) in patients (pts) with advanced melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475.

NCT01295827 MRK F. Stephen Hodi 3006^

A phase IB study of ipilimumab with peginterferon alfa-2b for patients with unresectable stages IIIB/C/IV melanoma. NCT01496807 MRK Ragini Reiney Kudchadkar

9098

Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL). NCT01295827 MRK Antoni Ribas LBA9000^ Dose-seeking and efficacy study of combination BRAFi and high-dose IFN (HDI) for therapy of advanced melanoma. NCT01943422 MRK Diwakar Davar TPS9110 Phase 1 study of MEDI4736, an anti-PD-L1 antibody, in combination with dabrafenib and trametinib or trametinib alone in patients with unresectable or metastatic melanoma.

NCT02027961 MedImmune Michael S. Gordon TPS9108

Phase I/II study of weekly LOC-paclitaxel (LOC-pac) injection in patients (pts) with metastatic melanoma (MM). NCT01039844 Luitpold Pharmaceuticals

Rodabe Navroze Amaria 9053

A phase I study with LTX-315, an immunogenic cell death inducer, in patients with transdermally accessible tumors. NCT01058616 Lytix Biopharma Paal Brunsvig 3067 Preliminary results from a phase 1/2 study of INCB024360 combined with ipilimumab (IPI) in patients (pts) with melanoma.

NCT01604889 Incyte Geoffrey Thomas Gibney

3010

COMBI-d: A randomized, double-blinded, Phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAFV600E/Kmutation-positive cutaneous melanoma.

NCT01072175 GSK/Novartis Georgina V. Long 9011^

Updated overall survival (OS) for BRF113220, a phase 1-2 study of dabrafenib (D) alone versus combined dabrafenib and trametinib (D+T) in pts with BRAF V600 mutation-positive (+) metastatic melanoma (MM).

NCT01072175 GSK Keith Flaherty 9010^

Long-term safety and overall survival update for BREAK-2, a phase 2, single-arm, open-label study of dabrafenib in previously treated metastatic melanoma (NCT01153763).

NCT01153763 GSK Paolo Antonio Ascierto 9034

A phase II single-arm study of pazopanib and paclitaxel as first-line treatment for patients with advanced melanoma. NCT01107665 GSK John P. Fruehauf 9036 Phase II, open-label study of dabrafenib plus trametinib in patients with BRAF mutation-positive melanoma brain metastases: A GSK-sponsored trial.

NCT02039947 GSK Michael A. Davies TPS9106

Pharmacokinetic and pharmacodynamic analysis of preoperative therapy with dabrafenib alone and in combination with trametinib in patients with BRAF mutation–positive melanoma with metastases to the brain (BRV116521).

NCT01978236 GSK Michael A. Davies TPS9112

Biomarker study evaluating the combination of dabrafenib (D) with trametinib (T) versus the combination after 8 weeks of monotherapy with dabrafenib or trametinib in patients with metastatic and unresectable stage IIIC or IV melanoma: GSK study 116613.

GSK Christine Mateus TPS9114^

Phase II study of vemurafenib in patients with locally advanced, unresectable stage IIIc or metastatic melanoma and activating exon 15BRAF mutations other than V600E.

NCT01586195 Genentech Sigrun Hallmeyer 9075^

A pilot trial of hu14.18-IL2 in patients with completely resectable recurrent stage III or stage IV melanoma. NCT00590824 EMD Serono Mark R. Albertini 9044 Targeted modified IL-2 (NHS-IL2, MSB0010445) combined with stereotactic body radiation in advanced melanoma patients after progression on ipilimumab: Assessment of safety, clinical, and biologic activity in a phase 2a study.

NCT01973608 EMD Serono Howard L Kaufman TPS9107

















































http://clinicaltrials.gov/show/nct00590824





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ASCO 2014 – MELANOMA SELECTED ABSTRACTS TRIAL DATA COMPANY FIRST AUTHOR ABSTRACT First-in-human, pharmacokinetic (PK), and pharmacodynamics (PD) phase I study of Debio1143 (AT-406) in patients with advanced cancer: Final results.

NCT01078649 Debiopharm, Ascent Therapeutics

Herbert Hurwit 2532

Phase 2, multicenter, safety and efficacy study of pidilizumab in patients with metastatic melanoma. NCT01435369 CureTech Michael B. Atkins 9001 Immunologic activity of an activating anti-CD27 antibody (CDX-1127) in patients (pts) with solid tumors. NCT01460134 Celldex

Therapeutics Jeffrey R. Infante 3027

Final overall survival from a phase 3 trial of nab-paclitaxel versus dacarbazine (DTIC) in chemotherapy-naive patients with metastatic melanoma.

NCT00864253 Celgene Evan Hersh 9045

Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial.

NCT00730639 BMS, Ono Pharma F. Stephen Hodi 9002

Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).

NCT01024231 BMS, Ono Pharma Mario Sznol LBA9003^

Updated survival, toxicity, and biomarkers of nivolumab with/without peptide vaccine in patients naive to, or progressed on, ipilimumab (IPI).

NCT01176461 BMS Jeffrey S. Weber 3009

Safety and clinical activity of combining systemic ipilimumab with isolated limb infusion in patients with in-transit melanoma.

NCT01323517 BMS Charlotte Eielson Ariyan 9078

Phase II study of low-dose cyclophosphamide and ipilimumab in metastatic melanoma. NCT01740401 BMS Anna C. Pavlick e20025 Ipilimumab for stage unresectable III/IV melanoma: Brazilian experience in an expanded access program. NCT00495066 BMS Rafael Schmerling e20045 Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

EudraCT 2007-001974-10

BMS Alexander M. Eggermont

LBA9008

Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

NCT00769704 BioVex/Amgen Howard L Kaufman 9008a

Patterns of durable response with intralesional talimogene laherparepvec (T-VEC): Results from a phase III trial in patients with stage IIIb-IV melanoma.

NCT00769704 BioVex/Amgen Merrick I. Ross 9026

A phase 1 study of MEDI4736, an anti–PD-L1 antibody, in patients with advanced solid tumors. NCT01693562 AstraZeneca Jose Lutzky 3001^ Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. NCT01693562 AstraZeneca Neil Howard Segal 3002^ Primary analysis of a phase 1b multicenter trial to evaluate safety and efficacy of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) in previously untreated, unresected stage IIIB-IV melanoma.

NCT01740297 Amgen Igor Puzanov 9029^

Open-label, multicenter, single-arm phase II study (DeCOG-Trial) to further evaluate the efficacy and safety of ipilimumab in patients with cutaneous melanoma and rare subgroups.

NCT01355120 Lisa Zimmer 9031

Phase II multicentric uncontrolled national trial assessing the efficacy of nilotinib in the treatment of advanced melanomas with c-KIT mutation or amplification.

NCT01168050 Celeste Lebbe 9032

Phase II study evaluating ipilimumab as a single agent in the first-line treatment of adult patients (Pts) with metastatic uveal melanoma (MUM): The GEM-1 trial.

EudraCT 2010-024415-14

Jose Maria Piulats Rodriguez

9033






























https://www.clinicaltrialsregister.eu/ctr-search/search?query=2007-001974-10



























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ASCO 2014 – MELANOMA SELECTED ABSTRACTS TRIAL DATA COMPANY FIRST AUTHOR ABSTRACT Treatment patterns and outcomes in BRAF V600E mutant melanoma patients with brain metastases receiving vemurafenib in the real-world setting.

Geoffrey Thomas Gibney

9035

Incidence and characteristics of melanoma brain metastases appearing during vemurafenib treatment. Lucie Peuvrel 9042 Biochemotherapy with interleukin-2 for metastatic melanoma: Long-term results in 100 patients.

David R. Minor 9047

Randomized, double-blind phase II trial of NY-ESO-1 ISCOMATRIX vaccine and ISCOMATRIX adjuvant alone in patients with resected stage IIc, III, or IV malignant melanoma.

NCT00199901 Jonathan S. Cebon 9050

Improved median overall survival (OS) in patients with metastatic melanoma (mM) treated with high-dose (HD) IL-2: Analysis of the PROCLAIM 2007-2012 national registry.

Gregory A. Daniels 9054

Ipilimumab in acral melanoma: A retrospective review. Douglas Buckner Johnson

9056

Vemurafenib treatment in patients with BRAF-mutated melanoma failing MEK inhibition with trametinib. Helen Gogas 9061 A randomized phase II study of ipilimumab (IPI) with carboplatin and paclitaxel (CP) in patients with unresectable stage III or IV metastatic melanoma (MM).

NCT01676649 Rahima Jamal 9066

Predictive importance of ulceration on the efficacy of adjuvant interferon-a (IFN): An individual patient data (IPD) meta-analysis of 15 randomized trials in more than 7,500 melanoma patients (pts).

Stefan Suciu 9067

Adjuvant therapy with pegylated interferon alfa-2a (PEG-IFN) versus low-dose interferon alfa-2a (IFN) in patients with malignant melanoma in stages IIa (T3a): IIIb (AJCC 2002)—Decog-trial.

NCT00204529 Thomas K. Eigentler 9071

The Memorial Sloan Kettering Cancer Center (MSKCC) experience of systemic therapy in mucosal melanoma. Christiana Bitas 9073 Assessment of overall survival from time of metastastasis in mucosal, uveal, and cutaneous melanoma. Michael Andrew

Postow 9074

Outcome with stereotactic radiosurgery (SRS) and ipilimumab (Ipi) for malignant melanoma brain metastases (mets). Sana Shoukat 9076 Lesion-specific patterns of response and progression with anti-PD-1 treatment in metastatic melanoma (MM). Megan Kate Lyle 9077 Treatment with tumor-infiltrating lymphocytes (TIL) in metastatic melanoma and clinical benefit regardless of site of origin, mutation status, or prior checkpoint blockade.

Isabella Claudia Glitza 9079

On-demand Gamma Knife combined with BRAF inhibitors for the treatment of melanoma brain metastases. Caroline Gaudy-Marqueste

9083

Phase I/II study of resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with melanoma. NCT00821652 Rachel Lubong Sabado 9086 Efficacy of two ipilimumab (IPI) doses (10 vs. 3 mg/kg) in Alberta, Canada, tertiary cancer centers. Richard M. Lee-Ying 9090 Integration of melanoma genotyping in clinical care. Ines Esteves Domingues

Pires Da Silva 9095

Safety and immunologic correlates of allogeneic melanoma GVAX (MelGVAX), a genetically engineered whole-cell melanoma vaccine.

NCT01435499 Evan J. Lipson e20001

Tumor response and patient survival after intralesional therapy with low-dose GM-CSF and IL-2 in metastatic and primary cutaneous melanoma: An exploratory study.

E. George Elias e20002






































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ASCO 2014 – MELANOMA SELECTED ABSTRACTS TRIAL DATA COMPANY FIRST AUTHOR ABSTRACT O-mel-sora: A national multicenter phase II trial of sorafenib in metastatic uveal melanoma. EudraCT 2010-

022527-29 Frédéric Mouriaux e20004

The experience of administration of high-dose recombinant interleukin-2 in combination with chemotherapy in the management of disseminated skin melanoma.

Olga Streltsova e20008

The Mayo Clinic experience with the use of kinase inhibitors (KIs), ipilimumab, and bevacizumab in the treatment of metastatic ocular melanoma.

Justin Moser e20011

Survival of thick melanoma in a Spanish university hospital: Analysis of 15 years experience. Jose Antonio Aviles Izquierdo

e20012

Primary malignant melanoma of the esophagus: Clinical features, signaling pathway, management, and survival. Xuan Wang e20015 Prognostic factors for disease-free survival of ethnic Chinese patients with ocularmelanoma. Xi Nan Sheng e20016 Salvage therapy for metastatic acral or mucosal melanoma: Efficacy and safety analysis of nab-paclitaxel/carboplatin combined with bevacizumab in c-kit/BRAF wild-type pts.

Chuan Liang Cui e20017

Pharmacogenetic investigation of dabrafenib efficacy in a meta-analysis of three melanoma studies. Diptee A Kulkarni e20018 Fotemustine (F) in the treatment of malignant melanoma nonassociated with B-RAF mutations. Yana V Svetitskaya e20033 Single-center experience in French Temporary Authorization for Use (TAU) metastatic melanoma program with ipilimumab.

Francois Chasset e20034

Prognosis of patients with very thin cutaneous melanoma: The good, the bad, and the miscoded.

Phyllis A. Gimotty e20044

Patients (p) with advanced melanoma receiving rescue surgery (RS), BRAF inhibitors (BRAFi), immunotherapy (IT) or chemotherapy (CT) in an off-protocol, routine clinical setting.

Jose Luis Cuadra-Urteaga

e20046

Number of sites of metastasis (NSM) and progression-free survival (PFS) in patients (PTS) with melanoma treated with ipilimumab (IPI).

Monique Celeste Tavares

e20048

Outcome predictors in patients receiving high-dose interleukin-2 therapy for the treatment of metastatic melanoma and renal cell carcinoma.

Jeremy D. Whyman e20055

Phase I-II study of the combination vemurafenib plus peg-interferon in advanced melanoma patients harboring the V600BRAF mutation.

NCT01959633 Paolo Antonio Ascierto TPS9105

BeyPro1: A phase II single-arm study for the treatment after recurrence of advanced melanoma patients harboring the V600BRAF mutation and pretreated with vemurafenib, with the association of vemurafenib plus fotemustine.

NCT01983124 Paola Queirolo TPS9109

Open-label, multicenter, single-arm phase II study (DeCOG-Trial) to further evaluate the efficacy and safety of ipilimumab in patients with cutaneous melanoma and rare subgroups.

NCT01355120 Lisa Zimmer 9031

Phase II multicentric uncontrolled national trial assessing the efficacy of nilotinib in the treatment of advanced melanomas with c-KIT mutation or amplification.

NCT01168050 Celeste Lebbe 9032

The GERMELATOX DeCOG-trial: German melanoma patients and their attitude toward toxicity during adjuvant interferon treatment.

Katharina C. Kaehler TPS9113^

Source: 2014 ASCO Meeting Abstracts Database






































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