A Multi -Institutional Phase 2 Study of Single Agent ...
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18WCGIC Poster presented at: Purpose : Primary Objective: o Response rate per RECIST 1.1 Secondary Objectives: o PFS and OS o Grade 3/4 toxicities Exploratory Objectives: o Fresh tissue biopsies were requested for all patients treated at MDACC (pre- and on-treatment). • Immunophenotyping with IHC and flow cytometry (Morris et al, AACR 2016). o Serial blood samples were drawn on all patients. Background : Worldwide, it is estimated that SCCA will develop in > 27,000 patients (pts). 20% of pts will develop metastatic (met) disease for which there is no standard approach. o We have previously demonstrated that > 90% of metastatic SCCA is associated with HPV. Nivolumab (Nivo), a monoclonal antibody targeting PD-1 on T cells, promotes immune-mediated anti-tumor activity of T cells against HPV-positive cells in vitro. o We proceeded to conduct the first phase II trial of Nivolumab in previously treated met SCCA pts. Methods : All pts were required to be immunotherapy naïve; > 1 prior metastatic treatment; presence or absence of PD-L1 expression. If HIV+, CD4 count > 300/uL. A Simon two-stage phase II trial (Ho: p < .05, Ha: p ≥ .20) was conducted. Pts received Nivo (3 mg/kg) IV every 2 weeks. Optional pre- treatment and on-treatment tissue and plasma samples, and post progression (plasma samples only) were collected, including cfDNA. Results: 39 pts consented; 37 patients are evaluable for toxicity and intent to treat (May 2015 - October 2015). o 2 pts were HIV+ The median age is 56 years (range: 51-64); M:F is 11:28. Median number of prior therapies: 2 (range 1-7). Median number of cycles provided: 6 (range 1-23). RR: 2 CR’s; 7 PR’s resulted in an ORR of 24%. Median PFS: 3.9M Grade 3 toxicities: Anemia (N=2) and rash, hypothyroidism, fatigue (N=1 each). No grade 4 toxicities were noted. Conclusions: There is an increased annual incidence of the HPV- associated malignancy, SCC of the anal canal. NCI9673 is the first prospective phase II trial to be completed in refractory metastatic SCCA. Single agent nivolumab was well tolerated and fulfilled the primary endpoint of response. o Note: No unexpected SAE’s were noted in HIV+ pts. Rapid enrollment was feasible via the NCI ETCTN and provided an opportunity for clinical trial development for a “rare” cancer. An amendment is underway to evaluate combination therapy. Acknowledgements : All participating patients and ETCTN sites MDACC : • IMT Platform (P Sharma, J Allison, J Blando, L Vence, P Hwu, and C Logethetis), Armeen Mahvash (IR), Amir Mehdizadeh and Nataly Silva Grant Support: • MDACC HPV-Associated Malignancies Moonshot • Anal Cancer Foundation • E.B. Anal Cancer Fund • Anonymous MDACC philanthropic donor A Multi-Institutional Phase 2 Study of Single Agent Nivolumab in Previously Treated Metastatic Squamous Cell Carcinoma of the Anal Canal (SCCA) C Eng 1 , V Morris 1 , K. Ciombor 2 , M.E. Salem 3 , H. Nimeiri 4 , S. Iqbal 5 , P. Singh 6 , B. Polite 7 , D. Deming 8 , E. Chan 9 , J.L. Wade 10 , T.S. Bekaii-Saab 2 , R.A. Wolff 1 1 The University of Texas MD Anderson Cancer Center, Houston, TX; 2 The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Columbus, OH; 3 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC; 4 Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; 5 University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA; 6 Washington University, Siteman Cancer Center, St. Louis, MO; 7 The University of Chicago, Chicago, IL; 8 University of Wisconsin Hospitals and Clinics, Madison, WI; 9 Vanderbilt University Medical Center, Nashville, TN; 10 Cancer Care Center of Decatur, Decatur, IL Future Directions for Met SCCA: Clinical Trials - o Treatment naïve • InterAACT/ECOG EA#2133: Randomized phase II study of cytotoxic chemotherapy (NCT02051868) - International Rare Cancers Initiative (IRCI) o Refractory • ADXS11-001: Live listeria vaccine with fusion protein of HPV16/E7 • Amendment of NCI9673 in development (ETA: Fall 2016) o HIV+ pts • HIV Consortium phase I study (NCT02408861) Continued clinical trial enrollment is crucial in the hopes of obtaining an FDA indication for the “rare” cancer of metastatic squamous cell carcinoma of the anal canal. Pre-treatment: May 2015 Post-treatment: June 2016 Flow Cytometry Imaging Clinical Response: 22--O Cathy Eng DOI: 10.3252/pso.eu.18wgic.2016 Clinical Other
Transcript of A Multi -Institutional Phase 2 Study of Single Agent ...
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WC
GIC
Poster presented at:
Purpose:
Primary Objective:
o Response rate per RECIST 1.1
Secondary Objectives:
o PFS and OS
o Grade 3/4 toxicities
Exploratory Objectives:
o Fresh tissue biopsies were requested for all patients
treated at MDACC (pre- and on-treatment).
• Immunophenotyping with IHC and flow
cytometry (Morris et al, AACR 2016).
o Serial blood samples were drawn on all patients.
Background:
Worldwide, it is estimated that SCCA will develop in > 27,000 patients (pts).
20% of pts will develop metastatic (met) disease for which there is no standard approach.
o We have previously demonstrated that > 90% of metastatic SCCA is associated with HPV.
Nivolumab (Nivo), a monoclonal antibody targeting PD-1 on T cells, promotes immune-mediated anti-tumor activity of T cells against HPV-positive cells in vitro.
o We proceeded to conduct the first phase II trial of Nivolumab in previously treated met SCCA pts.
Methods:
All pts were required to be immunotherapy naïve; > 1 prior metastatic treatment; presence or absence of PD-L1 expression. If HIV+, CD4 count > 300/uL.
A Simon two-stage phase II trial (Ho: p < .05, Ha: p ≥ .20) was conducted.
Pts received Nivo (3 mg/kg) IV every 2 weeks. Optional pre-treatment and on-treatment tissue and plasma samples, and post progression (plasma samples only) were collected, including cfDNA.
Results:
39 pts consented; 37 patients are evaluable for toxicity and intent to treat (May 2015 - October 2015).
o 2 pts were HIV+ The median age is 56 years (range: 51-64); M:F is 11:28. Median number of prior therapies: 2 (range 1-7). Median number of cycles provided: 6 (range 1-23). RR: 2 CR’s; 7 PR’s resulted in an ORR of 24%. Median PFS: 3.9M Grade 3 toxicities: Anemia (N=2) and rash, hypothyroidism,
fatigue (N=1 each). No grade 4 toxicities were noted.
Conclusions:
There is an increased annual incidence of the HPV-associated malignancy, SCC of the anal canal.
NCI9673 is the first prospective phase II trial to be completed in refractory metastatic SCCA.
Single agent nivolumab was well tolerated and fulfilled the primary endpoint of response.
o Note: No unexpected SAE’s were noted in HIV+ pts.
Rapid enrollment was feasible via the NCI ETCTN and provided an opportunity for clinical trial development for a “rare” cancer.
An amendment is underway to evaluate combination therapy.
Acknowledgements:
All participating patients and ETCTN sitesMDACC:
• IMT Platform (P Sharma, J Allison, J Blando, L Vence, P Hwu, and C Logethetis), Armeen Mahvash (IR), Amir Mehdizadeh and Nataly Silva
Grant Support: • MDACC HPV-Associated Malignancies Moonshot• Anal Cancer Foundation • E.B. Anal Cancer Fund • Anonymous MDACC philanthropic donor
A Multi-Institutional Phase 2 Study of Single Agent Nivolumab in Previously Treated Metastatic Squamous Cell Carcinoma of the Anal Canal (SCCA)
C Eng1, V Morris1, K. Ciombor2, M.E. Salem3, H. Nimeiri4, S. Iqbal5, P. Singh6, B. Polite7, D. Deming8, E. Chan9, J.L. Wade10, T.S. Bekaii-Saab2, R.A. Wolff1
1The University of Texas MD Anderson Cancer Center, Houston, TX; 2The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Columbus, OH; 3Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC; 4Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; 5University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA; 6Washington University, Siteman Cancer Center, St. Louis, MO; 7The University of Chicago, Chicago, IL; 8University of Wisconsin Hospitals and Clinics, Madison, WI; 9Vanderbilt University Medical Center, Nashville, TN;
10Cancer Care Center of Decatur, Decatur, IL
Future Directions for Met SCCA:
Clinical Trials -
o Treatment naïve
• InterAACT/ECOG EA#2133: Randomized phase II study of cytotoxic chemotherapy (NCT02051868) - International Rare Cancers Initiative (IRCI)
o Refractory
• ADXS11-001: Live listeria vaccine with fusion protein of HPV16/E7
• Amendment of NCI9673 in development (ETA: Fall 2016)
o HIV+ pts
• HIV Consortium phase I study (NCT02408861)
Continued clinical trial enrollment is crucial in the hopes of obtaining an FDA indication for the “rare” cancer of metastatic squamous cell carcinoma of the anal canal.
Pre-treatment: May 2015
Post-treatment: June 2016
Flow Cytometry
Imaging
Clinical Response:
22--OCathy Eng DOI: 10.3252/pso.eu.18wgic.2016
Clinical Other
