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3334 Durable complete responses (CR) in patients (pts) with stage IIIB-IV melanoma treated with talimogene laherparepvec (T-VEC) in OPTiM
S676
Abstracts
lymph node had a CR and remains disease free, and one pt had a CR in an injected neck lymph node, but has slowly progressed in a lung metastasis. None of these 3 pts received any additional treatment after completing HF10 injections. Conclusions: Intratumoral HF10 serial injections are safe and welltolerated. Related AE included chills, fatigue and injection site reactions. Efficacy evaluation (overall and local) suggests that HF10 has both local and systemic antitumor activity in metastatic melanoma and can result in delayed responses. HF10 is a potential new treatment option for melanoma pts, and a Phase II study of intratumoral HF10 combined with systemic immunotherapy (ipilimumab) in unresectable metastatic melanoma pts is underway. Conflict of interest: Corporate-sponsored Research: This research is sponsor by Takara Bio Inc. 3334 POSTER Durable complete responses (CR) in patients (pts) with stage IIIB-IV melanoma treated with talimogene laherparepvec (T-VEC) in OPTiM R.H.I. Andtbacka1 , H. Kaufman2 , F. Collichio3 , T. Amatruda4 , J. Nemunaitis5 , J. Chesney6 , I. Puzanov7 , K. Harrington8 , Y. Zhang9 , L. Chen9 , M. Shilkrut10 , M. Ross11 . 1 Huntsman Cancer Institute at the University of Utah, Surgical Oncology Department of Surgery, Salt Lake City, UT, USA; 2 Rutgers Cancer Institute of New Jersey, Surgery, New Brunswick, NJ, USA; 3 The University of North Carolina Chapel Hill, School of Medicine, Hematology Oncology, Chapel Hill, NC, USA; 4 Minnesota Oncology, Medical Oncology, Fridley, MN, USA; 5 Mary Crowley Cancer Research Cneter, Medical Oncology, Dallas, TX, USA; 6 University of Louisville, Medical Oncology/Hematology, Louisville, KY, USA; 7 Vanderbilt University Medical Center, Hematology/Oncology, Nashville, TN, USA; 8 The Institute of Cancer Research/The Royal Marsden Hospital, Biological Cancer Therapies, London, United Kingdom; 9 Amgen Inc., Global Biostatistical Science, Thousand Oaks, CA, USA; 10 Amgen Inc., Oncology/Clinical Development, Thousand Oaks, CA, USA; 11 MD Anderson Cancer Center, Surgical Oncology, Houston, TX, USA Background: T-VEC is a systemically active HSV-1 derived injectable oncolytic immunotherapy. In OPTiM, a phase 3 trial in 436 pts with unresected stage IIIB-IV melanoma, intralesional T-VEC improved durable response rate (continuous partial response [PR] or CR 6 mo; primary endpoint) from 2% to 16% and overall response rate from 6% to 26% vs subcutaneous GM-CSF. Median overall survival (OS, secondary endpoint) was 23.3 mo in the T-VEC arm and 18.9 mo in the GM-CSF arm (HR = 0.79, 95% CI: 0.62–1.00; P = 0.051). Here we report on pts that achieved CR with T-VEC in OPTiM. Materials and Methods: A retrospective analysis of OPTiM final OS data (cutoff Aug 2014; included pts who continued treatment after tumor response analysis at Dec 2012) was conducted to identify pts who achieved a CR (investigator assessment by modified WHO criteria) with T-VEC. Kaplan–Meier method was used to estimate CR duration, recurrence-free survival (RFS; from CR to recurrence, death due to disease progression, or subsequent anti-cancer therapy), and OS. Results: Of 287 evaluable pts treated with T-VEC, 50 (17%) achieved CR. Compared to pts with PR or no response, pts with CR were older, had lower total tumor burden, had a higher proportion of pts with stage IIIB,
IIIC, and IVM1a melanoma without elevated LDH, and received T-VEC as a 1st-line therapy (Table). Median (Q1-Q3) time to achieve a CR was 8.6 (6.0–13.6) mo. 32 (64%) pts had a durable CR continuous for 6 mo. Median (95% CI) RFS was not reached, with 84% (70−92) and 72% (57−83) estimated being recurrence-free at 1- and 3-y after achieving CR, respectively. Median (95% CI) OS for pts with CR was not reached, with 96% (85−99) and 89% (74−95) being alive at 3- and 5-y, respectively. Conclusion: Treatment with T-VEC resulted in CR in 17% of pts seen in all stages of melanoma but most commonly in pts with earlier stages and lower tumor burden disease. The majority of pts with durable CR achieved prolonged OS without recurrence. T-VEC provides a potential new treatment option for pts with unresected regionally and distantly metastatic melanoma with limited visceral disease. Conflict of interest: Ownership: L. Chen, Y. Zhang, M. Shilkrut: Amgen. Advisory Board: R.H.I. Andtbacka: Amgen, Merck. H. Kaufman: Alkermes, Amgen, EMD Serono, Merck, Prometheus, Sanofi. F. Collichio: Amgen. J. Chesney: Amgen. I. Puzanov: Amgen. K. Harrington: Amgen, Merck, Viralytics. M. Ross: Merck, Amgen. Board of Directors: None. Corporatesponsored Research: R.H.I. Andtbacka: Amgen, Viralytics, Takara. H. Kaufman: Amgen, BMS, EMD Serono, Merck, Prometheus. F. Collichio: BMS, Novartis, Amgen, Morphotek. T. Amatruda: Amgen, BMS. J. Chesney: Amgen. I. Puzanov: Amgen, Roche, Genentech, GSK, Merck. K. Harrington: Oncolytics Biotech. Genelux, Viralytics. M. Ross: Amgen, GSK, Provectos, Neostem. Other Substantive Relationships: K. Harrington: Honoraria from Amgen and Merck. L. Chen, Y. Zhang, M. Shilkrut: Amgen employees. 3335 POSTER SPOTLIGHT/POSTER Intralesional administration of Coxsackievirus A21 (CVA21) oncolytic virus immunotherapy in patients with advanced melanoma induces durable tumor responses R.H.I. Andtbacka1 , B. Curti2 , H.L. Kaufman3 , G.A. Daniels4 , J.J. Nemunaitis5 , L.E. Spitler6 , S. Hallmeyer7 , J. Lutzky8 , S. Schultz9 , E.D. Whitman10 , K. Zhou11 , R. Karpathy12 , J.I. Weisberg12 , D. Shafren12 . 1 Huntsman Cancer Institute, University of Utah, Surgical Oncology, Salt Lake City, UT, USA; 2 Providence Cancer Center, Medical Oncology, Portland, OR, USA; 3 Rush University Medical Center, Surgical Oncology, Chicago, IL, USA; 4 UCSD Moores Cancer Center, Medical Oncology, La Jolla, CA, USA; 5 Mary Crowley Cancer Research Center, Medical Oncology, Dallas, TX, USA; 6 Northern California Melanoma Center, Medical Oncology, San Francisco, CA, USA; 7 Oncology Specialists SC, Medical Oncology, Park Ridge, IL, USA; 8 Mount Sinai Comprehensive Cancer Center, Medical Oncology, Miami Beach, FL, USA; 9 Indiana Cancer Center, Medical Oncology, Indianapolis, IN, USA; 10 Atlantic Melanoma Center, Surgical Oncology, Morristown, NJ, USA; 11 inVentiv Health Clinical, Research, Princeton, NJ, USA; 12 Viralytics Inc., Research, Sydney, Australia Background: CVA21 (CAVATAK)is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21. Intratumoral (IT) CVA21 injection can induce preferentialtumor cell infection, tumor immune-cell infiltration, up-regulation of interferon gamma response genes, cell lysis and enhancement of a systemic anti-tumor immune response. Pre-clinical studies in an immune-competent mouse model of melanoma have revealed
Table (abstract 3334).
Median age, years (Q1−Q3) ECOG PS, n (%) 0 1 Disease stage, n (%) IIIB IIIC IVM1a IVM1b IVM1c Elevated LDH, n (%) Median baseline total tumor burden*, cm2 (min−max) Line of therapy, n (%) 1st 2nd
CR (N = 50)
PR (N = 43)
No response (N = 194)
P-value
70 (60−78)
64 (53−77)
62 (53−71)
0.021 0.13
42 (84) 8 (16)
31 (72) 12 (28)
135 (70) 59 (30)
12 (24) 19 (38) 15 (30) 2 (4) 2 (4) 0 (0) 4.6 (0.3−38.3)
3 (7) 12 (28) 14 (33) 7 (16) 7 (16) 0 (0) 10.9 (0.6−280.6)
7 (4) 35 (18) 45 (23) 54 (28) 53 (27) 13 (7) 20.4 (0.6−350.0)
33 (66) 17 (34)
27 (63) 16 (37)
78 (40) 116 (60)
<0.0001
*Sum of the products of the 2 largest perpendicular diameters of index lesions at baseline.
0.041 <0.0001 <0.0001
Abstracts
lymph node had a CR and remains disease free, and one pt had a CR in an injected neck lymph node, but has slowly progressed in a lung metastasis. None of these 3 pts received any additional treatment after completing HF10 injections. Conclusions: Intratumoral HF10 serial injections are safe and welltolerated. Related AE included chills, fatigue and injection site reactions. Efficacy evaluation (overall and local) suggests that HF10 has both local and systemic antitumor activity in metastatic melanoma and can result in delayed responses. HF10 is a potential new treatment option for melanoma pts, and a Phase II study of intratumoral HF10 combined with systemic immunotherapy (ipilimumab) in unresectable metastatic melanoma pts is underway. Conflict of interest: Corporate-sponsored Research: This research is sponsor by Takara Bio Inc. 3334 POSTER Durable complete responses (CR) in patients (pts) with stage IIIB-IV melanoma treated with talimogene laherparepvec (T-VEC) in OPTiM R.H.I. Andtbacka1 , H. Kaufman2 , F. Collichio3 , T. Amatruda4 , J. Nemunaitis5 , J. Chesney6 , I. Puzanov7 , K. Harrington8 , Y. Zhang9 , L. Chen9 , M. Shilkrut10 , M. Ross11 . 1 Huntsman Cancer Institute at the University of Utah, Surgical Oncology Department of Surgery, Salt Lake City, UT, USA; 2 Rutgers Cancer Institute of New Jersey, Surgery, New Brunswick, NJ, USA; 3 The University of North Carolina Chapel Hill, School of Medicine, Hematology Oncology, Chapel Hill, NC, USA; 4 Minnesota Oncology, Medical Oncology, Fridley, MN, USA; 5 Mary Crowley Cancer Research Cneter, Medical Oncology, Dallas, TX, USA; 6 University of Louisville, Medical Oncology/Hematology, Louisville, KY, USA; 7 Vanderbilt University Medical Center, Hematology/Oncology, Nashville, TN, USA; 8 The Institute of Cancer Research/The Royal Marsden Hospital, Biological Cancer Therapies, London, United Kingdom; 9 Amgen Inc., Global Biostatistical Science, Thousand Oaks, CA, USA; 10 Amgen Inc., Oncology/Clinical Development, Thousand Oaks, CA, USA; 11 MD Anderson Cancer Center, Surgical Oncology, Houston, TX, USA Background: T-VEC is a systemically active HSV-1 derived injectable oncolytic immunotherapy. In OPTiM, a phase 3 trial in 436 pts with unresected stage IIIB-IV melanoma, intralesional T-VEC improved durable response rate (continuous partial response [PR] or CR 6 mo; primary endpoint) from 2% to 16% and overall response rate from 6% to 26% vs subcutaneous GM-CSF. Median overall survival (OS, secondary endpoint) was 23.3 mo in the T-VEC arm and 18.9 mo in the GM-CSF arm (HR = 0.79, 95% CI: 0.62–1.00; P = 0.051). Here we report on pts that achieved CR with T-VEC in OPTiM. Materials and Methods: A retrospective analysis of OPTiM final OS data (cutoff Aug 2014; included pts who continued treatment after tumor response analysis at Dec 2012) was conducted to identify pts who achieved a CR (investigator assessment by modified WHO criteria) with T-VEC. Kaplan–Meier method was used to estimate CR duration, recurrence-free survival (RFS; from CR to recurrence, death due to disease progression, or subsequent anti-cancer therapy), and OS. Results: Of 287 evaluable pts treated with T-VEC, 50 (17%) achieved CR. Compared to pts with PR or no response, pts with CR were older, had lower total tumor burden, had a higher proportion of pts with stage IIIB,
IIIC, and IVM1a melanoma without elevated LDH, and received T-VEC as a 1st-line therapy (Table). Median (Q1-Q3) time to achieve a CR was 8.6 (6.0–13.6) mo. 32 (64%) pts had a durable CR continuous for 6 mo. Median (95% CI) RFS was not reached, with 84% (70−92) and 72% (57−83) estimated being recurrence-free at 1- and 3-y after achieving CR, respectively. Median (95% CI) OS for pts with CR was not reached, with 96% (85−99) and 89% (74−95) being alive at 3- and 5-y, respectively. Conclusion: Treatment with T-VEC resulted in CR in 17% of pts seen in all stages of melanoma but most commonly in pts with earlier stages and lower tumor burden disease. The majority of pts with durable CR achieved prolonged OS without recurrence. T-VEC provides a potential new treatment option for pts with unresected regionally and distantly metastatic melanoma with limited visceral disease. Conflict of interest: Ownership: L. Chen, Y. Zhang, M. Shilkrut: Amgen. Advisory Board: R.H.I. Andtbacka: Amgen, Merck. H. Kaufman: Alkermes, Amgen, EMD Serono, Merck, Prometheus, Sanofi. F. Collichio: Amgen. J. Chesney: Amgen. I. Puzanov: Amgen. K. Harrington: Amgen, Merck, Viralytics. M. Ross: Merck, Amgen. Board of Directors: None. Corporatesponsored Research: R.H.I. Andtbacka: Amgen, Viralytics, Takara. H. Kaufman: Amgen, BMS, EMD Serono, Merck, Prometheus. F. Collichio: BMS, Novartis, Amgen, Morphotek. T. Amatruda: Amgen, BMS. J. Chesney: Amgen. I. Puzanov: Amgen, Roche, Genentech, GSK, Merck. K. Harrington: Oncolytics Biotech. Genelux, Viralytics. M. Ross: Amgen, GSK, Provectos, Neostem. Other Substantive Relationships: K. Harrington: Honoraria from Amgen and Merck. L. Chen, Y. Zhang, M. Shilkrut: Amgen employees. 3335 POSTER SPOTLIGHT/POSTER Intralesional administration of Coxsackievirus A21 (CVA21) oncolytic virus immunotherapy in patients with advanced melanoma induces durable tumor responses R.H.I. Andtbacka1 , B. Curti2 , H.L. Kaufman3 , G.A. Daniels4 , J.J. Nemunaitis5 , L.E. Spitler6 , S. Hallmeyer7 , J. Lutzky8 , S. Schultz9 , E.D. Whitman10 , K. Zhou11 , R. Karpathy12 , J.I. Weisberg12 , D. Shafren12 . 1 Huntsman Cancer Institute, University of Utah, Surgical Oncology, Salt Lake City, UT, USA; 2 Providence Cancer Center, Medical Oncology, Portland, OR, USA; 3 Rush University Medical Center, Surgical Oncology, Chicago, IL, USA; 4 UCSD Moores Cancer Center, Medical Oncology, La Jolla, CA, USA; 5 Mary Crowley Cancer Research Center, Medical Oncology, Dallas, TX, USA; 6 Northern California Melanoma Center, Medical Oncology, San Francisco, CA, USA; 7 Oncology Specialists SC, Medical Oncology, Park Ridge, IL, USA; 8 Mount Sinai Comprehensive Cancer Center, Medical Oncology, Miami Beach, FL, USA; 9 Indiana Cancer Center, Medical Oncology, Indianapolis, IN, USA; 10 Atlantic Melanoma Center, Surgical Oncology, Morristown, NJ, USA; 11 inVentiv Health Clinical, Research, Princeton, NJ, USA; 12 Viralytics Inc., Research, Sydney, Australia Background: CVA21 (CAVATAK)is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21. Intratumoral (IT) CVA21 injection can induce preferentialtumor cell infection, tumor immune-cell infiltration, up-regulation of interferon gamma response genes, cell lysis and enhancement of a systemic anti-tumor immune response. Pre-clinical studies in an immune-competent mouse model of melanoma have revealed
Table (abstract 3334).
Median age, years (Q1−Q3) ECOG PS, n (%) 0 1 Disease stage, n (%) IIIB IIIC IVM1a IVM1b IVM1c Elevated LDH, n (%) Median baseline total tumor burden*, cm2 (min−max) Line of therapy, n (%) 1st 2nd
CR (N = 50)
PR (N = 43)
No response (N = 194)
P-value
70 (60−78)
64 (53−77)
62 (53−71)
0.021 0.13
42 (84) 8 (16)
31 (72) 12 (28)
135 (70) 59 (30)
12 (24) 19 (38) 15 (30) 2 (4) 2 (4) 0 (0) 4.6 (0.3−38.3)
3 (7) 12 (28) 14 (33) 7 (16) 7 (16) 0 (0) 10.9 (0.6−280.6)
7 (4) 35 (18) 45 (23) 54 (28) 53 (27) 13 (7) 20.4 (0.6−350.0)
33 (66) 17 (34)
27 (63) 16 (37)
78 (40) 116 (60)
<0.0001
*Sum of the products of the 2 largest perpendicular diameters of index lesions at baseline.
0.041 <0.0001 <0.0001