Immune checkpoint inhibitors can be coadministered as a fixed-ratio combination (FRC) or administered as sequential infusions (ASI). Two randomized, open-label trials compared nivolumab + ipilimumab as a FRC versus ASI in patients with melanoma or renal cell carcinoma.
CheckMate 742 was a Phase 3b study in patients with advanced or metastatic melanoma who received nivolumab 1 mg/kg and ipilimumab 3 mg/kg either concurrently as an FRC or sequentially as ASI every 3 weeks. CheckMate 800 was a Phase 2 study in patients with advanced or metastatic renal cell carcinoma who received nivolumab 3 mg/kg and ipilimumab 1 mg/kg either concurrently as an FRC or sequentially as ASI every 3 weeks. The primary endpoint was the incidence of adverse events (AEs) in the Broad Scope Medical Dictionary for Regulatory Activities (MedDRA) Anaphylactic Reaction Standardized MedDRA Queries (SMQ) occurring within 2 days after dosing. Secondary endpoints included incidence of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ.
There was no clinically relevant difference in safety between FRC and ASI as measured by the primary endpoint in either study; odds ratio (95% CI) of 0.87 (0.30-2.49) and 1.0 (0.30-3.39) for CheckMate 742 and CheckMate 800, respectively. No AEs were reported in the Narrow Scope MedDRA Anaphylactic Reaction SMQ in either study. One death from drug toxicity occurred in CheckMate 742.
Both studies met their primary endpoint. The safety profiles of nivolumab + ipilimumab as FRC or ASI were acceptable and manageable.
NCT02905266 and NCT03029780 for CheckMate 742 and CheckMate 800, respectively.
Cancer. 2025 Jul 15 [Epub]
Alexander M Menzies, Pamela Salman, Osvaldo Arén Frontera, David Pook, Christopher M Hocking, Yousef Zakharia, Howard Gurney, Craig Gedye, Jeffrey C Goh, Bijoy Telivala, Jean-Jacques Grob, Céleste Lebbé, Luis de la Cruz Merino, Laurent Machet, Eve-Marie Neidhardt, Anila Qureshi, Fareeda Hosein, Lora Hamuro, Burcin Simsek, Asim Amin
Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia., Fundación Arturo López Pérez, Santiago, Chile., Centro Investigación Clínica Bradford Hill, Santiago, Chile., Cabrini Hospital, Malvern, Victoria, Australia., Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia., University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA., Westmead Hospital and Macquarie University, Sydney, New South Wales, Australia., Calvary Mater Newcastle, Waratah, New South Wales, Australia., Royal Brisbane and Women's Hospital and Queensland University of Technology (QUT), Brisbane, Queensland, Australia., Cancer Specialists of North Florida, Jacksonville, Florida, USA., Hôpital de la Timone, Marseille, France., Université Paris Cité, INSERM U976, Dermato-Oncologie and CIC AP-HP Hôpital Saint Louis, Cancer Institute APHP, Nord-Université Paris Cité, Paris, France., Cancer Immunotherapy, Clinical Oncology Department, Biomedicine Institute of Seville (IBIS)/CSIC, University Hospital Virgen Macarena and School of Medicine, University of Seville, Seville, Spain., Centre Hospitalier Régional Universitaire de Tours, Université de Tours, Tours, France., Centre Léon Bérard, Lyon, France., Bristol Myers Squibb, Princeton, New Jersey, USA., Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, USA.