Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma.

Autor:	Chesney JA; UofL Health-Brown Cancer Center, University of Louisville, Louisville, KY., Ribas A; Jonsson Comprehensive Cancer Center at the University of California Los Angeles, Los Angeles, CA., Long GV; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.; Royal North Shore and Mater Hospitals, Sydney, NSW, Australia., Kirkwood JM; UPMC Hillman Cancer Center, Pittsburgh, PA., Dummer R; University Hospital of Zurich, Zurich, Switzerland., Puzanov I; Roswell Park Comprehensive Cancer Center, Buffalo, NY., Hoeller C; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Gajewski TF; University of Chicago Medical Center, Chicago, IL., Gutzmer R; Medizinische Hochschule Hannover, Hannover, Germany.; Mühlenkreiskliniken Minden, Ruhr University Bochum, Bochum, Germany., Rutkowski P; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Demidov L; N.N. Blokhin Russian Cancer Research Center, Moscow, Russia., Arenberger P; University Hospital Královské Vinohrady, Prague, Czech Republic., Shin SJ; Division of Oncology, Yonsei University College of Medicine, Seoul, Korea., Ferrucci PF; Biotherapy of Tumors Unit, Department of Experimental Oncology, European Institute of Oncology, IRCCS, Milan, Italy., Haydon A; Department of Medical Oncology, Alfred Hospital, Melbourne, Australia., Hyngstrom J; Huntsman Cancer Institute, University of Utah Health, Salt Lake City, UT., van Thienen JV; Netherlands Cancer Institute, Amsterdam, the Netherlands., Haferkamp S; Department of Dermatology, University Hospital Regensburg, Regensburg, Germany., Guilera JM; Department of Dermatology, Barcelona University, Barcelona, IDIBAPS, CIBER de Enfermedades Raras ISCIII, Madrid, Spain., Rapoport BL; The Medical Oncology Centre of Rosebank, Johannesburg, South Africa.; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa., VanderWalde A; Department of Hematology/Oncology, West Cancer Center & Research Institute, Memphis, TN., Diede SJ; Merck & Co, Inc, Kenilworth, NJ., Anderson JR; Merck & Co, Inc, Kenilworth, NJ., Treichel S; Amgen Inc, South San Francisco, CA., Chan EL; Amgen Inc, Thousand Oaks, CA., Bhatta S; Amgen Inc, Thousand Oaks, CA., Gansert J; Amgen Inc, Thousand Oaks, CA., Hodi FS; Dana-Farber Cancer Institute, Boston, MA., Gogas H; National and Kapodistrian University of Athens, Athens, Greece.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Jan 20; Vol. 41 (3), pp. 528-540. Date of Electronic Publication: 2022 Aug 23.
DOI:	10.1200/JCO.22.00343
Abstrakt:	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 × 10 6 plaque-forming unit (PFU) followed by ≤ 4 × 10 8 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.
Databáze:	MEDLINE
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