Background: In preliminary findings from the recurrent or metastatic cervical cancer cohort of CheckMate 358, nivolumab showed durable anti-tumour responses, and the combination of nivolumab plus ipilimumab showed promising clinical activity. Here, we report long-term outcomes from this cohort., Methods: CheckMate 358 was a phase 1-2, open-label, multicohort trial. The metastatic cervical cancer cohort enrolled patients from 30 hospitals and cancer centres across ten countries. Female patients aged 18 years or older with a histologically confirmed diagnosis of squamous cell carcinoma of the cervix with recurrent or metastatic disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and up to two previous systemic therapies were enrolled into the nivolumab 240 mg every 2 weeks group, the randomised groups (nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks [NIVO3 plus IPI1] or nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks for four cycles then nivolumab 240 mg every 2 weeks [NIVO1 plus IPI3]), or the NIVO1 plus IPI3 expansion group. All doses were given intravenously. Patients were randomly assigned (1:1) to NIVO3 plus IPI1 or NIVO1 plus IPI3 via an interactive voice response system. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal, or for up to 24 months. The primary endpoint was investigator-assessed objective response rate. Anti-tumour activity and safety were analysed in all treated patients. This study is registered with ClinicalTrials.gov (NCT02488759) and is now completed., Findings: Between October, 2015, and March, 2020, 193 patients were recruited in the recurrent or metastatic cervical cancer cohort of CheckMate 358, of whom 176 were treated. 19 patients received nivolumab monotherapy, 45 received NIVO3 plus IPI1, and 112 received NIVO1 plus IPI3 (45 in the randomised group and 67 in the expansion group). Median follow-up times were 19·9 months (IQR 8·2-44·8) with nivolumab, 12·6 months (7·8-37·1) with NIVO3 plus IPI1, and 16·7 months (7·2-27·5) with pooled NIVO1 plus IPI3. Objective response rates were 26% (95% CI 9-51; five of 19 patients) with nivolumab, 31% (18-47; 14 of 45 patients) with NIVO3 plus IPI1, 40% (26-56; 18 of 45 patients) with randomised NIVO1 plus IPI3, and 38% (29-48; 43 of 112 patients) with pooled NIVO1 plus IPI3. The most common grade 3-4 treatment-related adverse events were diarrhoea, hepatic cytolysis, hyponatraemia, pneumonitis, and syncope (one [5%] patient each; nivolumab group), diarrhoea, increased gamma-glutamyl transferase, increased lipase, and vomiting (two [4%] patients each; NIVO3 plus IPI1 group), and increased lipase (nine [8%] patients) and anaemia (seven [6%] patients; pooled NIVO1 plus IPI3 group). Serious treatment-related adverse events were reported in three (16%) patients in the nivolumab group, 12 (27%) patients in the NIVO3 plus IPI1 group, and 47 (42%) patients in the pooled NIVO1 plus IPI3 group. There was one treatment-related death due to immune-mediated colitis in the NIVO1 plus IPI3 group., Interpretation: Nivolumab monotherapy and nivolumab plus ipilimumab combination therapy showed promise in the CheckMate 358 study as potential treatment options for recurrent or metastatic cervical cancer. Future randomised controlled trials of nivolumab plus ipilimumab or other dual immunotherapy regimens are warranted to confirm treatment benefit in this patient population., Funding: Bristol Myers Squibb and Ono Pharmaceutical., Competing Interests: Declaration of interests AO reports receiving grants from AbbVie, Ability Pharmaceuticals, Advaxis, Agenus, Aprea Therapeutics, AstraZeneca, Beigene, Belgian Gynaecological Oncology Group (BGOG), Bristol Myers Squibb, Clovis Oncology, Corcept Therapeutics, Eisai, F Hoffmann-La Roche, Grupo Español de Investigación en Cáncer de Ovario (GEICO), Immunogen, Iovance Biotherapeutics, Lilly, Medimmune, Merck Healthcare, Merck Sharp & Dohme, Millennium Pharmaceuticals, Mundipharma Research, Novartis Farmacéutica, Regeneron Pharmaceuticals, Seagen, Seattle Genetics, Sutro Biopharma, Tesaro, University Health Network, and Werastem; consultant or advisory fees from Agenus, AstraZeneca Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceutical, Eisai Europe, EMD Serono, F Hoffmann-La Roche, GlaxoSmithKline (GSK), GOG, Immunogen, Medison Pharma, Merck Sharp & Dohme de España, Mersana Therapeutics, Novocure, Pharma Mar, prIME Oncology, Roche Farma, Sattucklabs, and Sutro Biopharma; honoraria from Edizioni Minerva Medica, ESMO, and Doctaforum Servicios; and travel accommodations from AstraZeneca, Clovis, GSK, PharmaMar, and Roche. KM reports receiving research grants from Clovis, Genentech, GSK, Lilly, PTC Therapeutics, and Verastem; consultant or advisory fees from AstraZeneca, Aravive, Alkermes, Addi, Blueprint Pharma, Clovis, Eisai, GSK, Genentech/Roche, Hengrui, Immunogen, Inxmed, IMab, Lilly, Mereo, Mersana, Merck, Myriad, Novartis, Novocure, OncXerna, Onconova, Tarveda, VBL Therapeutics, and Verastem; honoraria from AstraZeneca, Great Debates and Updates, GSK, Immunogen, Medscape, PRIME, and RTP; travel accommodations from AstraZeneca; and is a GOG Partners Associate Director. TM reports receiving grants from Bayer Biocompatibles, MSD; and consulting fees from Adaptimmune, AstraZeneca, Bristol Myers Squibb, Eisai, Ipsen, and Roche. LAD reports receiving consultant or advisory fees from MSD. AA reports receiving speaker fees from Bristol Myers Squibb. CDL reports receiving speaker fees from Bristol Myers Squibb, Genentech, Novartis, and Oncosec; and research funding from BMS, Genentech, Novartis, and Oncosec. VB reports receiving institutional financial support for clinical trials from AbbVie, ACEO, Adaptimmune, Amcure, Amgen, Amunix, Astellas, AstraZeneca, BeiGene, Bicycle, BMS, Boehringer Ingelheim, Boston Therapeutics, CytomX, Daiichi, DebioPharm, Dynavax, Genentech/Roche, Genmab, GSK, Incyte, Innovio, Ipsen, Janssen, Kura, Lilly, Loxo, Macrogenics, Menarini, Merck, Mersana, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, ORCA, Pfizer, PharmaMar, Principia, PsiOxus, PUMA, Ribbon, Ryvu, Sanofi, Seattle Genetics, Taiho, Takeda, Tesaro, Transgene, Regeneron, Rigontec, Seagen, Spectrum, Synthon, Urogen, and Zenith; consultant or advisory fees from CytomX Therapeutics, Guidepoint, Ideaya Biosciences, Janssen, Lilly, Loxo Therapeutics, Oncoart, and Puma Biotechnology; honoraria from Eli Lilly, Gedefo, Getthi, MSD, SOLTI, and TACTICS; and travel or accommodation support from Bayer. WHS reports receiving grants from AstraZeneca, Bristol Myers Squibb, Genentech, Merck, and Novartis; and consultant or advisory fees from Bristol Myers Squibb, ION, Merck, Pfizer, and Regeneron. MT reports receiving grants from Bayer and Ono Pharmaceuticals; consultant or advisory fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Genmab, Janssen, Lilly, MSD, Merck Biopharma, Ono Pharmaceuticals, and Pfizer; and honoraria from Bayer, Bristol Myers Squibb, Eisai, Lilly, Merck Biopharma, Ono Pharmaceuticals, and Rakuten Medical. SLT reports receiving grants from Bristol Myers Squibb; and consultant or advisory fees from AstraZeneca and PathAI; and reports receipt of research grants from Compugen, and consulting fees from Amgen, Bristol Myers Squibb, Compugen, and Janssen Pharmaceuticals for an immediate family member. MM reports leadership role fees from Centro Oncologico Internacional. AMA reports receiving consultant or advisory fees from Amgen, AstraZeneca, and Eli Lilly; being a Principal Investigator for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Janssen, and MSD; and speaker's bureau fees from GSK; and other fees from Roche. TAK is an employee and stockholder of Bristol Myers Squibb. CC is an employee and stockholder of Bristol Myers Squibb. ML is an employee of Syneos Health, which provides consulting services to Bristol Myers Squibb. CG-B is an employee and stockholder of Bristol Myers Squibb. XW was previously an employee of Bristol Myers Squibb and reports receiving stock options from Bristol Myers Squibb. RWN reports receiving research funding from Bristol Myers Squibb, GSK/Tesaro, Gynecologic Oncology Group, Mersana, and OncoMed Sutro Bio; speaker's bureau from Seagen; and consultant or advisory fees from Agenus, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Eisai, Genelux, GOG Partners, GSK/Tesaro, Immunogen, Laekna, MSD, OncoMed, Seagen, and Sutro Bio. JL-PG and JCP declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)