Patterns of response with talimogene laherparepvec in combination with ipilimumab or ipilimumab alone in metastatic unresectable melanoma

Abstract

Talimogene laherparepvec (T-VEC) has demonstrated efficacy for unresectable melanoma. We explored response patterns from a phase 2 study evaluating patients with unresectable stage IIIB-IVM1c malignant melanoma who received T-VEC plus ipilimumab or ipilimumab alone. Patients with objective response per modified irRC were evaluated for pseudo-progression (single ≥25% increase in tumour burden before response). Patients without pseudo-progression were classified by whether they responded within or after 6 months of treatment start; those with pseudo-progression were classified by whether pseudo-progression was due to increase in existing lesions or development of new lesions. Overall, 39% (n = 38/98) in the combination arm and 18% (n = 18/100) in the ipilimumab arm had an objective response. Eight responders (combination, n = 7 [18.4%]; ipilimumab, n = 1 [5.6%]) had pseudo-progression; most occurred by week 12 and were caused by an increase in existing lesions. These data reinforce use of T-VEC through initial progression when combined with checkpoint inhibitors.Trial Registration NCT01740297 (ClinicalTrials.gov; date of registration, December 4, 2012); 2012-000307-32 (ClinicalTrialsRegister.eu; date of registration, May 13, 2014).

Conflict of interest statement

J.C. has received honoraria, consulting and/or advisory fees, and travel and accommodations expenses from Amgen; research funding from Amgen, Iovance, and Bristol-Myers Squibb; and has received reimbursement for service on a scientific advisory panel for Replimune. I.P. has received honoraria, consulting and/or advisory fees, and travel and accommodations expenses from Amgen. F.C. has received consulting fees from Amgen through a consulting agreement that ended in 2018, and institutional research funding from Amgen and Novartis. M.M. has served on the GIST advisory board for Blueprint Solutions and on an advisory board for Amgen. A.H. has received research funding, consulting fees, and honoraria from Novartis, Amgen, Bristol-Myers Squibb, MSD/Merck, Pierre Fabre, Provectus, and Roche; research funding and consulting fees from Merck Serono, Philogen, and Regeneron; consulting fees and speakers’ honoraria from Sanofi-Aventis, and consulting fees from OncoSec and Philogen. L.C. and A.S. are employees of and own stock in Amgen. C.G. has received honoraria and consulting and/or advisory fees from Amgen, Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche; research funding from Bristol-Myers Squibb, Novartis, and Roche; and travel and accommodations expenses from Amgen, Bristol-Myers Squibb, Merck Sharpe & Dohme, and Novartis. P.S. has nothing to disclose. J.M. has received honoraria and consulting and/or advisory fees from Boehringer Ingelheim, EMD Serono, Pfizer, Merck, and Amgen; research funding from Amgen, Novartis, Merck, Polynoma, AstraZeneca, Immunocore, Macrogenics, and Incyte; and travel and accommodation expenses from Merck, EMD Serono, and Boehringer Ingelheim.

Figures

Fig. 1

Patient incidence of pseudo-progression. OR objective response