Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial

• DOI: 10.1136/jitc-2022-006270
• Publication Date: 2023-05-04T15:01:43Z
• Authors: Jason A Chesney; Igor Puzanov; Frances A Collichio; Parminder Singh; Mohammed M Milhem; John Glaspy; Omid Hamid; Merrick Ross; Philip Friedlander; Claus Garbe; Theodore Logan; Axel Hauschild; Celeste Lebbé; Harshada Joshi; Wendy Snyder; Janice M Mehnert
• Keywords: Clinical endpoint

Talimogene laherparepvec (T-VEC) plus ipilimumab has demonstrated greater antitumor activity versus alone, without additional toxicity, in patients with advanced melanoma. Here, we report the 5-year outcomes from a randomized phase II study. These data provide longest efficacy and safety follow-up for melanoma treated combination of an oncolytic virus checkpoint inhibitor.Eligible unresectable stage IIIB‒IV were 1:1 to receive T-VEC or alone. was administered intralesionally at 106 plaque-forming units (PFU)/mL week 1, followed by 108 PFU/mL 4 every 2 weeks thereafter. Ipilimumab (3 mg/kg 3 weeks; ≤4 doses) intravenously starting 1 arm 6 arm. The primary end point investigator-assessed objective response rate (ORR) per immune-related criteria; key secondary points included durable (DRR), duration (DOR), progression-free survival (PFS), overall (OS), safety.Overall, 198 (n=98) (n=100). improved ORR (35.7% vs 16.0%; OR 2.9; 95% CI 1.5 5.7; p=0.003). DRR 33.7% 13.0% (unadjusted 3.4; 1.7 7.0; descriptive p=0.001), respectively. Among responders, median DOR 69.2 months (95% 38.5 not estimable) reached ipilimumab. Median PFS 13.5 6.4 (HR 0.78; 0.55 1.09; p=0.14). Estimated OS 54.7% 43.9 64.2) 48.4% 37.9 58.1) Forty-seven (48.0%) 65 (65.0%) arms, respectively, received subsequent therapies. No new signals reported.At follow-up, rates observed durable. This is first controlled study inhibitor that meets its point.Trial registration number: NCT01740297.