Survival, safety, and response patterns in a phase 1b multicenter trial of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) in previously untreated, unresected stage IIIB-IV melanoma.

Melanoma/Skin Cancers
Session Type and Session Title: 
Poster Session, Melanoma/Skin Cancers
Abstract Number: 


Poster Board Number: 
Board #306
J Clin Oncol 33, 2015 (suppl; abstr 9063)
Igor Puzanov, Mohammed M. Milhem, Robert Hans Ingemar Andtbacka, David R. Minor, Omid Hamid, Ai Li, Jeffrey Chou, Howard Kaufman; Vanderbilt University Medical Center, Nashville, TN; University of Iowa Hospitals and Clinics, Iowa City, IA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; California Pacific Melanoma Center, San Francisco, CA; The Angeles Clinic and Research Institute, Los Angeles, CA; Amgen Inc., Thousand Oaks, CA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ

Abstract Disclosures


Background: T-VEC is an HSV-derived oncolytic immunotherapy designed to induce systemic antitumor immunity. In a phase 3 melanoma study, T-VEC monotherapy significantly improved durable response rate (DRR, ≥ 6 month response) vs GM-CSF (16% vs 2%, P < 0.0001; Andtbacka et al. ASCO 2013), and median OS was 4.4 months longer for T-VEC vs GM-CSF (23.3 vs 18.9 months; HR = 0.79, 95% CI: 0.62-1.00; P= 0.051; Kaufman et al, ASCO 2014). Combining T-VEC to promote tumor-derived antigen release with an immune checkpoint inhibitor may enhance efficacy compared to either agent alone. The phase 1b portion of this phase 1b/2 combination study (NCT01740297) completed enrollment and met its primary objective with no dose-limiting toxicities (DLTs) and an objective response rate (ORR) of 56% (Puzanov et al. ASCO 2014). Methods: Key inclusion criteria included stage IIIB-IV melanoma; no prior systemic treatment; measurable disease; and ≥ 1 injectable cutaneous, subcutaneous, or nodal lesion. T-VEC was given intralesionally at ≤ 4 mL of 106 PFU/mL at week 1, then 108 PFU/mL at week 4, and then Q2W. Ipi 3 mg/kg Q3W was given as 4 infusions starting week 6. T-VEC continued until DLT, intolerance, all injectable tumors disappeared, or disease progression (PD) per immune-related response criteria (irRC). Results: The data cutoff was Dec 22, 2014 with all patients at least 17 months from start of treatment. 18 patients received T-VEC+ipi; grade 3/4 treatment-emergent AEs occurred in 32% and grade 3/4 immune-related AEs occurred in 2 patients with no treatment-related deaths. Per irRC, ORR was 56% (33% CR) and DRR was 44%. Median time to response was 5.3 months (range 2.6-5.7). Median progression-free survival (PFS) was 10.6 months (2.6-19.3+). Median overall survival (OS) was not reached; 12-month and 18-month survival were 72.2% and 67%. On a lesion level, 24 and 11 of 35 injected index lesions and 8 and 5 of 16 uninjected index lesions regressed ≥ 50% and 100%, respectively. Conclusions: At > 17 months, T-VEC+ipi continued to demonstrate durable responses with 2/3 of patients alive at 18 months and no new safety signals. Phase 2 (ipi vs T-VEC+ipi) is ongoing. Clinical trial information: NCT01740297