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Title: Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules.
Austin Authors: Long, Georgina V;Robert, Caroline;Butler, Marcus O;Couture, Felix;Carlino, Matteo S;O'Day, Steven;Atkinson, Victoria;Cebon, Jonathan S ;Brown, Michael P;Dalle, Stephane;Hill, Andrew G;Gibney, Geoffrey T;McCune, Steven;Menzies, Alexander M;Niu, Cuizhen;Ibrahim, Nageatte;Homet Moreno, Blanca;Diab, Adi
Affiliation: MSD China
Melanoma Institute Australia, The University of Sydney, and Mater and Royal North Shore Hospitals.
INSERM U981, Institut Gustave Roussy
Medical Oncology, Princess Margaret Cancer Centre
Université Laval
Medicine, Melanoma Institute Australia, The University of Sydney, Blacktown Hospital, and Crown Princess Mary Cancer Centre, Westmead Hospital
John Wayne Cancer Institute at Providence Saint John's Health Center
Division of Cancer Services, Princess Alexandra Hospital
Olivia Newton-John Cancer Research Institute
Department of Medical Oncology, Royal Adelaide Hospital
iNSERM 590, Claude Bernard Lyon University
Oncology, Tasman Oncology Research
Medical Oncology, Georgetown Lombardi Comprehensive Cancer Center
Medical Oncology, WellStar Health System
Melanoma Institute Australia, The University of Sydney and Royal North Shore and Mater Hospitals
Oncology, Merck Research Laboratories
Merck & Co., Inc
Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
Issue Date: 1-Jul-2021
Date: 2021-07-01
Publication information: Clinical Cancer Research 2021; 27(19): 5280-5288
Abstract: Standard-dose pembrolizumab plus alternative-dose ipilimumab (1 mg/kg Q3W for 4 doses) was tolerable and had robust antitumor activity in advanced melanoma in cohort B of the phase 1 KEYNOTE-029 study. Cohort C evaluated standard-dose pembrolizumab with two other alternative ipilimumab regimens. Patients with treatment-naive unresectable stage III/IV melanoma were randomly assigned 1:1 to pembrolizumab 200 mg Q3W for {less than or equal to}24 months plus ipilimumab 50 mg Q6W for 4 doses (PEM200+IPI50), or the same pembrolizumab regimen plus ipilimumab 100 mg Q12W for 4 doses (PEM200+IPI100). Primary end points were incidence of grade 3-5 treatment-related adverse events (TRAEs) and objective response rate (ORR) per RECIST v1.1 by independent central review. Per protocol-defined thresholds, grade 3-5 TRAE incidence {less than or equal to}26% indicated meaningful toxicity reduction and ORR {greater than or equal to}48% indicated no decrease in efficacy versus data reported for other PD-1 inhibitor/ipilimumab combinations. Median follow-up on February 18, 2019, was 16.3 months in PEM200+IPI50 (N=51) and 16.4 months in PEM200+IPI100 (N=51). Grade 3-5 TRAEs occurred in 12 (24%) patients in PEM200+IPI50 and 20 (39%) in PEM200+IPI100. One patient in PEM200+IPI50 died from treatment-related autoimmune myocarditis. Immune-mediated AEs or infusion reactions occurred in 21 (42%) patients in PEM200+IPI50 and 28 (55%) in PEM200+IPI100. ORR was 55% in PEM200+IPI50; 61% in PEM200+IPI100. Pembrolizumab 200 mg Q3W plus ipilimumab 50 mg Q6W or 100 mg Q12W demonstrated antitumor activity above the predefined threshold; pembrolizumab plus ipilimumab 50 mg Q6W had lower incidence of grade 3-5 TRAEs than the predefined threshold, suggesting a reduction in toxicity.
DOI: 10.1158/1078-0432.CCR-21-0793
ORCID: 0000-0001-8894-3545
Journal: Clinical Cancer Research
PubMed URL: 34210681
Type: Journal Article
Appears in Collections:Journal articles

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