Journal article
Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma
Journal of clinical oncology, Vol.36(17), pp.1658-1667
06/10/2018
DOI: 10.1200/JCO.2017.73.7379
PMCID: PMC6075852
PMID: 28981385
Abstract
Purpose
We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor.
Methods
Patients with unresectable stages IIIB to IV melanoma, with no more than one prior therapy if BRAF wild-type, no more than two prior therapies if BRAF mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression were randomly assigned 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone. Talimogene laherparepvec treatment began in week 1 (first dose, <= 4 mL x 10(6) plaque-forming units/mL; after 3 weeks, <= 4 mL x 10(8) plaque-forming units/mL every 2 weeks). Ipilimumab (3 mg/kg every 3 weeks; up to four doses) began week 1 in the ipilimumab alone arm and week 6 in the combination arm. The primary end point was objective response rate evaluated by investigators per immune-related response criteria.
Results
One hundred ninety-eight patients were randomly assigned to talimogene laherparepvec plus ipilimumab (n = 98), or ipilimumab alone (n = 100). Thirty-eight patients (39%) in the combination arm and 18 patients (18%) in the ipilimumab arm had an objective response (odds ratio, 2.9; 95% CI, 1.5 to 5.5; P = .002). Responses were not limited to injected lesions; visceral lesion decreases were observed in 52% of patients in the combination arm and 23% of patients in the ipilimumab arm. Frequently occurring adverse events (AEs) included fatigue (combination, 59%; ipilimumab alone, 42%), chills (combination, 53%; ipilimumab alone, 3%), and diarrhea (combination, 42%; ipilimumab alone, 35%). Incidence of grade <= 3 AEs was 45% and 35%, respectively. Three patients in the combination arm had fatal AEs; none were treatment related.
Conclusion
The study met its primary end point; the objective response rate was significantly higher with talimogene laherparepvec plus ipilimumab versus ipilimumab alone. These data indicate that the combination has greater antitumor activity without additional safety concerns versus ipilimumab. (c) 2017 by American Society of Clinical Oncology.
Details
- Title: Subtitle
- Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma
- Creators
- Jason Chesney - University of Louisville HospitalIgor Puzanov - Roswell Park Cancer InstituteFrances Collichio - University of North CarolinaParminder Singh - Mayo Clinic, Scottsdale AZ.Mohammed M. Milhem - University of IowaJohn Glaspy - University of California, Los AngelesOmid Hamid - Angeles Clinic and Research InstituteMerrick Ross - The University of Texas MD Anderson Cancer CenterPhilip Friedlander - Icahn School of Medicine at Mount SinaiClaus Garbe - University of TübingenTheodore F. Logan - Indiana UniversityAxel Hauschild - Kiel UniversityCeleste Lebbe - Université Paris CitéLisa Chen - AmgenJenny J. Kim - AmgenJennifer Gansert - AmgenRobert H. I. Andtbacka - University of UtahHoward L. Kaufman - Rutgers, The State University of New Jersey
- Resource Type
- Journal article
- Publication Details
- Journal of clinical oncology, Vol.36(17), pp.1658-1667
- Publisher
- Amer Soc Clinical Oncology
- DOI
- 10.1200/JCO.2017.73.7379
- PMID
- 28981385
- PMCID
- PMC6075852
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Number of pages
- 12
- Grant note
- P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Amgen
- Language
- English
- Date published
- 06/10/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359671702771
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