Caladrius SITC 2015 Poster: Superiority of dendritic cell vaccine vs tumor cell vaccine
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Superiority of dendritic cell vaccine vs tumor cell vaccine: Survival by stratification subsets in MACVAC randomized phase II trial of patient-specific vaccines utilizing antigens from autologous melanoma tumor cell lines Dillman RO, 1 McClay EF, 2 Amatruda TT, 3 Semeniuk, GB, 4 Haskins CE, 5 Weber RW, 6 Burtzo DM, 7 DePriest C, 8 Carbonell D, 1 Cornforth AN. 1 1 Caladrius BioSciences, Inc. Irvine, CA, USA, 2 California Cancer Associates for Research and Excellence (cCARE), Institute for Melanoma Research & Education, Encinitas CA., USA, 3 Minnesota Oncology, Fridley, MN., USA, 4 Orange Coast Oncology and Hematology, Newport Beach, CA., 5 New Mexico Cancer Center, Albuquerque, NM., USA, 6 St. Mary’s Medical Center and Sutter Health, San Francisco, CA., USA, 7 Pacific Shores Medical Group, Huntington Beach, CA. USA, 8 Franklin, TN., USA. The Society for Immunotherapy of Cancer (SITC) 30th Anniversary Annual Meeting & Associated Programs • November 4 - 8, 2015 Gaylord National Hotel & Convention Center • National Harbor, Maryland
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Transcript of Caladrius SITC 2015 Poster: Superiority of dendritic cell vaccine vs tumor cell vaccine
Superiority of dendritic cell vaccine vs tumor cell vaccine:
Survival by stratification subsets in MACVAC randomized phase II trial of patient-specific vaccines utilizing antigens from autologous
melanoma tumor cell lines
Dillman RO,1 McClay EF,2 Amatruda TT,3 Semeniuk, GB,4 Haskins CE,5 Weber RW,6 Burtzo DM,7 DePriest C,8 Carbonell D,1 Cornforth AN.1
1Caladrius BioSciences, Inc. Irvine, CA, USA, 2California Cancer Associates for Research and Excellence (cCARE), Institute for Melanoma Research & Education, Encinitas CA., USA, 3Minnesota Oncology, Fridley, MN., USA, 4Orange Coast Oncology and Hematology, Newport Beach, CA., 5New
Mexico Cancer Center, Albuquerque, NM., USA, 6St. Mary’s Medical Center and Sutter Health, San Francisco, CA., USA, 7Pacific Shores Medical Group, Huntington Beach, CA. USA, 8Franklin, TN., USA.
The Society for Immunotherapy of Cancer (SITC)30th Anniversary Annual Meeting & Associated Programs • November 4 - 8, 2015
Gaylord National Hotel & Convention Center • National Harbor, Maryland
Background and Rationale
• Most metastatic melanoma patients die within 2 years despite the addition of anti-checkpoint monoclonal antibodies and BRAF-MEK inhibitors
• Increased or enhanced recognition of tumor associated antigens (TAA) should result in long-term immune memory that improves long-term survival
• The best source of melanoma TAA may be short-term autologous tumor cell lines, because: - Melanoma cells contain numerous non-synonymous mutations that can result
in patient-specific antigens - Self-renewing proliferating cells are important for the persistence and spread
of metastases
Background and Rationale
• CLBS20 (aka NBS20 or DC-TC in previous randomized studies, USAN: eltrapuldencel-T) consists of autologous dendritic cells loaded with antigens from irradiated autologous melanoma cells that self-renew in vitro
• CLBS20 was injected with adjuvant GM-CSF (granulocyte macrophage colony-stimulating factor) weekly x 3, then up to monthly x 5 (maximum 8)
• CLBS20 has shown consistent, compelling results in phase II trials in patients with metastatic melanoma
Background and Rationale
- 2-yr overall survival (OS) 73%, 5-yr OS 50% in an open label, 54-patient trial - 2-yr OS 72% and superior OS compared to an irradiated tumor cell vaccine(TC) in
a 42-patient open-label randomized trial (p=0.007) - OS benefit demonstrated both in patients with no evidence of disease or
detectable distant metastatic disease at the time of treatment - Minimal toxicity: local injection site reactions
• One reference is incomplete and need only be listed once: Dillman RO, Cornforth AN, Nistor GI. Cancer stem cell antigen-based vaccines: the preferred strategy for active specific immunotherapy of metastatic melanoma? Expert Opin Biol Ther 13:643-656, 2013.
• Dillman RO. Melanoma Vaccines: Trials and Tribulations. Vaccine Dev Ther 3:57-78, 2013.• Dillman RO. Is vaccine research still relevant for metastatic melanoma? Melanoma Management 1:91-94, 2014.• Dillman RO. Melanoma Vaccines: Trials and Tribulations. Vaccine Dev Ther 3:57-78, 2013.• Dillman RO. Is vaccine research still relevant for metastatic melanoma? Melanoma Management 1:91-94, 2014.
Methods
• Patients: Those enrolled in the randomized phase II trial
• Purpose: To compare the treatment effects of CLBS20 (n=18) vs TC (n=24) in each of the subsets defined by the pre-randomization stratifications, which were based on whether patients had:
> Measurable or non-measurable disease as defined by RECIST
> Most advanced stage of disease stage IV or recurrent stage III
Treatment Effect Per Subsets Defined by Stratifications
in Phase 2
0
10
20
30
40
50
60
Measurable
Median OS (months)
0%
10%
20%
30%
40%
50%
60%
3-Year OS Rate (%)
0
10
20
30
40
50
60
70
Median OS (months)
0%
10%
20%
30%
40%
50%
60%
70%
80%
3-Year OS Rate (%)
8 patients
9 patients
10 patients
15 patients
8 patients
9 patients
10 patients
15 patients
3 patients
6 patients
15 patients
18 patients
3 patients
6 patients
15 patients
18 patients
>48.5
>60
Non-Measurable
Measurable Non-Measurable
Recurrent Stage III Stage IV
Recurrent Stage III Stage IV
CLBS20 Control
Treatment Effect Per Subsets Defined by Stratifications
in Phase 2CLBS20 Control0
10
20
30
40
50
60
Measurable
Median OS (months)
0%
10%
20%
30%
40%
50%
60%
3-Year OS Rate (%)
0
10
20
30
40
50
60
70
Median OS (months)
0%
10%
20%
30%
40%
50%
60%
70%
80%
3-Year OS Rate (%)
8 patients
9 patients
10 patients
15 patients
8 patients
9 patients
10 patients
15 patients
3 patients
6 patients
15 patients
18 patients
3 patients
6 patients
15 patients
18 patients
>48.5
>60
Non-Measurable
Measurable Non-Measurable
Recurrent Stage III Stage IV
Recurrent Stage III Stage IV
Treatment Effect Per Subsets Defined by Stratifications
in Phase 2CLBS20 Control
0
10
20
30
40
50
60
Measurable
Median OS (months)
0%
10%
20%
30%
40%
50%
60%
3-Year OS Rate (%)
0
10
20
30
40
50
60
70
Median OS (months)
0%
10%
20%
30%
40%
50%
60%
70%
80%
3-Year OS Rate (%)
8 patients
9 patients
10 patients
15 patients
8 patients
9 patients
10 patients
15 patients
3 patients
6 patients
15 patients
18 patients
3 patients
6 patients
15 patients
18 patients
>48.5
>60
Non-Measurable
Measurable Non-Measurable
Recurrent Stage III Stage IV
Recurrent Stage III Stage IV
Treatment Effect Per Subsets Defined by Stratifications
in Phase 2CLBS20 Control
0
10
20
30
40
50
60
Measurable
Median OS (months)
0%
10%
20%
30%
40%
50%
60%
3-Year OS Rate (%)
0
10
20
30
40
50
60
70
Median OS (months)
0%
10%
20%
30%
40%
50%
60%
70%
80%
3-Year OS Rate (%)
8 patients
9 patients
10 patients
15 patients
8 patients
9 patients
10 patients
15 patients
3 patients
6 patients
15 patients
18 patients
3 patients
6 patients
15 patients
18 patients
>48.5
>60
Non-Measurable
Measurable Non-Measurable
Recurrent Stage III Stage IV
Recurrent Stage III Stage IV
Results
At the time of this analysis:
• 29 patients were deceased
• 5 CLBS20 and 3 TC patients had been followed for 5 years;
• 5 patients (3 TC and 2 CLBS20) were alive but followed less than 5 years (minimum 3.5 years);
• No patients were lost to follow up
Conclusions
• CLBS20 immunotherapy was associated with improved survival in each of the four different subsets defined by the stratification variables
• CLBS20 has moved forward into a pivotal phase III trial sponsored by Caladrius Biosciences, Inc.
Contact
Robert O. Dillman, M.D., Vice President, OncologyCaladrius Biosciences, Inc.
18301 Von Karman Avenue, Suite 130 Irvine, California 92612
(949) 535-2418 e-mail: [email protected]
