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Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma
JA. Chesney, A. Ribas, GV. Long, JM. Kirkwood, R. Dummer, I. Puzanov, C. Hoeller, TF. Gajewski, R. Gutzmer, P. Rutkowski, L. Demidov, P. Arenberger, SJ. Shin, PF. Ferrucci, A. Haydon, J. Hyngstrom, JV. van Thienen, S. Haferkamp, JM. Guilera, BL....
Language English Country United States
Document type Randomized Controlled Trial, Multicenter Study, Clinical Trial, Phase III, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2004 to 1 year ago
Open Access Digital Library
from 1999-01-01
PubMed
35998300
DOI
10.1200/jco.22.00343
Knihovny.cz E-resources
- MeSH
- Double-Blind Method MeSH
- Humans MeSH
- Herpesvirus 1, Human * MeSH
- Melanoma * drug therapy MeSH
- Oncolytic Virotherapy * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase I MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
PURPOSE: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma. METHODS: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 106 plaque-forming unit (PFU) followed by ≤ 4 × 108 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis. RESULTS: Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm. CONCLUSION: T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.
Amgen Inc South San Francisco CA
Dana Farber Cancer Institute Boston MA
Department of Dermatology Medical University of Vienna Vienna Austria
Department of Dermatology University Hospital Regensburg Regensburg Germany
Department of Hematology Oncology West Cancer Center and Research Institute Memphis TN
Department of Immunology Faculty of Health Sciences University of Pretoria Pretoria South Africa
Department of Medical Oncology Alfred Hospital Melbourne Australia
Division of Oncology Yonsei University College of Medicine Seoul Korea
Huntsman Cancer Institute University of Utah Health Salt Lake City UT
Jonsson Comprehensive Cancer Center at the University of California Los Angeles Los Angeles CA
Maria Sklodowska Curie National Research Institute of Oncology Warsaw Poland
Medizinische Hochschule Hannover Hannover Germany
Melanoma Institute Australia The University of Sydney Sydney NSW Australia
Merck and Co Inc Kenilworth NJ
Mühlenkreiskliniken Minden Ruhr University Bochum Bochum Germany
N N Blokhin Russian Cancer Research Center Moscow Russia
National and Kapodistrian University of Athens Athens Greece
Netherlands Cancer Institute Amsterdam the Netherlands
Roswell Park Comprehensive Cancer Center Buffalo NY
Royal North Shore and Mater Hospitals Sydney NSW Australia
The Medical Oncology Centre of Rosebank Johannesburg South Africa
University Hospital Královské Vinohrady Prague Czech Republic
University Hospital of Zurich Zurich Switzerland
University of Chicago Medical Center Chicago IL
UofL Health Brown Cancer Center University of Louisville Louisville KY
References provided by Crossref.org
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