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.
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).
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%.Table: 60P
Response rates in pts who received ≥1 dose of T-VEC according to type of prior CPI therapy
|Response with T-VEC,* n (%)||Study 324||Study 325|
|Prior 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 response||1 (20)||0||3 (20)||4 (24)||1 (14)||1 (11)||5 (23)||6 (21)|
|Complete response (CR)||0||0||1 (7)||1 (6)||0||0||0||0|
|Partial response (PR)||1 (20)||0||2 (13)||3 (18)||1 (14)||1 (11)||5 (23)||6 (21)|
|Disease control (CR/PR/stable disease)||3 (60)||0||8 (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.
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
Legal entity responsible for the study
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.