Response rates with talimogene laherparepvec (T-VEC) monotherapy in patients (pts) with stage IIIB–IVM1c melanoma previously treated with checkpoint inhibitor (CPI) therapy: Retrospective analysis of two clinical trials
Authors: H. Gogas, R. Gutzmer, J. Malvehy, J.M. Mehnert, K. Liu, C.A. Pickett, W. Snyder, J. Chesney
Journal: Annals of Oncology (2018)

Background: In the phase 3 OPTiM trial, intratumoral T-VEC (an oncolytic immunotherapy) significantly improved the overall response rate (ORR) vs GM-CSF in pts with unresectable Stage IIIB–IVM1c melanoma (26% vs 6%; p < 0.001). Treatment options for pts with unresectable or metastatic melanoma who have previously received CPI therapy are limited. This retrospective analysis evaluated response to T-VEC in pts who had received prior CPI therapy. Methods: This analysis included data from two phase 2, single arm clinical trials of T-VEC monotherapy (Study 324 and Study 325). Both studies enrolled pts with unresectable or metastatic, stage IIIB–IVM1c melanoma, who were treated with T-VEC at the approved dose. Pts from these studies were included in the analysis if they had received prior pembrolizumab, nivolumab and/or ipilimumab (alone, sequentially or in combination). Results: Baseline characteristics of pts who had prior CPI therapy in Study 324 (N = 17)/Study 325 (N = 28), respectively, were: stage IIIB-IVM1a disease 71%/75%; BRAF wild-type 59%/61%; LDH ≤ULN 82%/75%. ORRs with T-VEC in Study 324 and Study 325 were 24% (4/17) and 21% (6/28), respectively (9 partial responses; 1 complete response; see Table). T-VEC-related adverse events (AEs) in CPI-experienced pts in Study 324/Study 325, respectively, were: Grade ≥3 AEs 18%/21%; serious AEs 18%/11%; AEs leading to permanent T-VEC discontinuation 12%/4%. Conclusions: Although this retrospective analysis has limitations, the ORR with T-VEC in pts previously treated with a CPI was consistent with the ORR observed with T-VEC in the phase 3 OPTiM trial. Types and incidence of AEs were consistent with the known safety profile of T-VEC. These data suggest that T-VEC demonstrates measurable activity for melanoma pts who have received a prior CPI and have an injectable metastasis. Clinical trial identification: NCT02366195; NCT02014441. Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc. Disclosure: H. Gogas: Advisor or consultant: Amgen, BMS, MSD, Novartis, Pierre Fabre, Roche. R. Gutzmer: Research support: J&J, Novartis & Pfizer; Consultant/served on speaker's bureau: Almirall Hermal, Amgen, BMS, GSK, MSD, Novartis & Roche; Speaker's bureau: Boehringer, Janssen, Merck-Serono, Pfizer. J. Malvehy: Consultant/advisor, honoraria: Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Roche, Swedish Orphan Biovitrum. J.M. Mehnert: Research grants: Sanofi, Merck, EMD Serono, Novartis, Polyoma, AstraZeneca, Immunocore; Consulting fees: Merck; Advisory board: Boehringer Ingelheim. K. Liu: Employee of Amgen. C.A. Pickett, W. Snyder: Employee and stock holder: Amgen. J. Chesney: Consulting fees/honoraria, travel/accommodation expenses: Amgen; Scientific advisory board member and speakers bureau member: Amgen.Table60P Response rates in pts who received ≥1 dose of T-VEC according to type of prior CPI therapyResponse with T-VEC,*Tumor response, according to modified WHO criteria using both clinical assessment and radiological imaging, was assessed at Weeks 12, 24 and then every ≤3 months; Pembrolizumab, nivolumab and/or ipilimumab (alone, sequentially or in combination). Only one pt in Study 324 received prior combination ipilimumab/nivolumab and was unevaluable. n (%)Study 324Study 325Prior pembrolizumab (N = 5)Prior nivolumab (N = 2)Prior ipilimumab (N = 15)Any prior CPI** (N = 17)Prior pembrolizumab (N = 7)Prior nivolumab (N = 9)Prior ipilimumab (N = 22)Any prior CPI** (N = 28)Objective response1 (20)03 (20)4 (24)1 (14)1 (11)5 (23)6 (21)Complete response (CR)001 (7)1 (6)0000Partial response (PR)1 (20)02 (13)3 (18)1 (14)1 (11)5 (23)6 (21)Disease control (CR/PR/stable disease)3 (60)08 (53)9 (53)3 (43)2 (22)9 (41)11 (39)*** Tumor response, according to modified WHO criteria using both clinical assessment and radiological imaging, was assessed at Weeks 12, 24 and then every ≤3 months; Pembrolizumab, nivolumab and/or ipilimumab (alone, sequentially or in combination). Only one pt in Study 324 received prior combination ipilimumab/nivolumab and was unevaluable. Open table in a new tab