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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, Stéphane;Hill, Andrew G;Gibney, Geoffrey T;McCune, Steven;Menzies, Alexander M;Niu, Cuizhen;Ibrahim, Nageatte;Moreno, Blanca Homet;Diab, Adi
Affiliation: Olivia Newton-John Cancer Research Institute
The University of Sydney, Sydney, New South Wales, Australia
Royal North Shore Hospital, Sydney, New South Wales, Australia
Cancer Clinical Trials Unit, Royal Adelaide Hospital and University of Adelaide, Adelaide, South Australia, Australia
The University of Sydney, Sydney, New South Wales, Australia
Department of Health, Tasman Oncology Research, Southport, Queensland, Australia
Department of Medicine, Westmead and Blacktown Hospitals, Melanoma Institute Australia
Department of Medical Oncology and Translational Research, Melanoma Institute Australia
University of Queensland, Division of Cancer Sciences, Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Brisbane, Queensland, Australia
Department of Medicine, Dermatology Service, Gustave Roussy, Paris-Saclay University, Villejuif, France
Department of Medical Oncology, The Princess Margaret Cancer Center and University of Toronto, Toronto, Ontario, Canada
Department of Hematology, CHU de Québec-Hôtel-Dieu de Québec, Québec City, Québec, Canada
Department of Medical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California
University of Lyon, Hospices Civils de Lyon, Cancer Research Center of Lyon, Lyon, France
Melanoma Disease Group, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC
Department of Clinical Research, Wellstar Health System, Marietta, Georgia
Department of Clinical Oncology, MSD China, Beijing, China
Department of Clinical Oncology, Merck & Co., Inc., Kenilworth, New Jersey
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Mater Hospital, Sydney, New South Wales, Australia
Issue Date: 1-Oct-2021
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) were 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 ≤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 (TRAE) and objective response rate (ORR) per RECIST v1.1 by independent central review. Per protocol-defined thresholds, grade 3-5 TRAE incidence ≤26% indicated meaningful toxicity reduction and ORR ≥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. See related commentary by Jameson-Lee and Luke, p. 5153.
DOI: 10.1158/1078-0432.CCR-21-0793
ORCID: 0000-0001-8894-3545
Journal: Clinical Cancer Research : An Official Journal of the American Association for Cancer Research
PubMed URL: 34210681
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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