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Clinical Trial
. 2025 Jul 15;131(14):e35962.
doi: 10.1002/cncr.35962.

Administration of nivolumab plus ipilimumab: Infusion of the fixed-ratio combination versus sequential infusions in two randomized controlled trials of metastatic melanoma (CheckMate 742) and renal cell carcinoma (CheckMate 800)

Alexander M Menzies  1 , Pamela Salman  2 , Osvaldo Arén Frontera  3 , David Pook  4 , Christopher M Hocking  5 , Yousef Zakharia  6 , Howard Gurney  7 , Craig Gedye  8 , Jeffrey C Goh  9 , Bijoy Telivala  10 , Jean-Jacques Grob  11 , Céleste Lebbé  12 , Luis de la Cruz Merino  13 , Laurent Machet  14 , Eve-Marie Neidhardt  15 , Anila Qureshi  16 , Fareeda Hosein  16 , Lora Hamuro  16 , Burcin Simsek  16 , Asim Amin  17
Affiliations
Clinical Trial

Administration of nivolumab plus ipilimumab: Infusion of the fixed-ratio combination versus sequential infusions in two randomized controlled trials of metastatic melanoma (CheckMate 742) and renal cell carcinoma (CheckMate 800)

Alexander M Menzies et al. Cancer. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Both studies met their primary endpoint. The safety profiles of nivolumab + ipilimumab as FRC or ASI were acceptable and manageable.

Trial registration numbers: NCT02905266 and NCT03029780 for CheckMate 742 and CheckMate 800, respectively.

Keywords: immune checkpoint inhibitors; ipilimumab; melanoma; nivolumab; renal cell carcinoma.

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Conflict of interest statement

Asim Amin has received payment for participating in a speaker bureau for Bristol Myers Squibb; advisory board payments from Bristol Myers Squibb, Eisai, and Pfizer. Anila Qureshi and Burcin Simsek are employees of Bristol Myers Squibb. Alexander M. Menzies has received advisory board fees from Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, QBiotics, and Roche. Bijoy Telivala, Christopher M. Hocking, Laurent Machet, and Osvaldo A. Frontera have nothing to declare. Craig Gedye has received consulting fees from BCAL Diagnostics, Cadex Genomics, and Novotech CRO. Céleste Lebbé has received institutional grants from Bristol Myers Squibb and Pierre Fabre; honoraria from Bristol Myers Squibb, MSD, and Pierre Fabre; support for attending meetings and/or travel from MSD and Pierre Fabre. David Pook has received honoraria from Bayer, Merck, and Pfizer; support for attending meetings and/or travel from Amgen, Astellas, Bayer, Bristol Myers Squibb, Janssen, MSD, and Pfizer. Eve‐Marie Neidhardt has received honoraria from Immunocore. Fareeda Hosein and Lora Hamuro are employees of and hold stock options in Bristol Myers Squibb. Howard Gurney has received advisory board fees from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, MSD, Merck Serono, and Pfizer. Jeffrey C. Goh has received medical writing support from Bristol Myers Squibb; advisory board fees from Bayer, Eisai and GSK; honoraria from Eisai, MSD, and Pfizer; support for attending meetings and/or travel from Bayer. Jean‐Jacques Grob has received consulting fees from Bristol Myers Squibb and Novartis; advisory board fees from Amgen, Bayer, Bristol Myers Squibb, MSD, Novartis, Philogen, Pierre Fabre, Sanofi, and Roche. Luis de la Cruz Merino has received institutional grants from Celgene, MSD, and Roche; honoraria from Bristol Myers Squibb, Celgene, MSD, and Novartis; support for attending meetings and/or travel from AstraZeneca, Celgene, and Pierre Fabre. Pamela Salman has received honoraria from AstraZeneca, Novartis, and Pfizer. Yousef Zakharia has received advisory board fees from Bristol Myers Squibb, Eisai, Exelixis, and Pfizer.

Figures

FIGURE 1
FIGURE 1
CONSORT study diagram. (A) CheckMate 742. (B) CheckMate 800. AE, adverse event; ASI, administration of sequential infusion; FRC, fixed‐ratio combination. aOne patient did not complete all four doses of the Part 1 treatment period because of study drug toxicity and was entered in the Part 2 maintenance phase. bAfter CheckMate 800 was terminated/closed, these patients were able to move to the CheckMate 8TT study.
See this image and copyright information in PMC

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