{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Overman MJ"],"funding":["Bristol Myers Squibb"],"pagination":["e008689"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11149130"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(5)"],"pubmed_abstract":["<h4>Background</h4>Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma. Here, we present the results from patients with MSI-H/dMMR metastatic CRC treated with nivolumab plus relatlimab in the CheckMate 142 study.<h4>Methods</h4>In this open-label, phase II study, previously treated patients with MSI-H/dMMR metastatic CRC received nivolumab 240 mg plus relatlimab 160 mg intravenously every 2 weeks. The primary end point was investigator-assessed objective response rate (ORR).<h4>Results</h4>A total of 50 previously treated patients received nivolumab plus relatlimab. With median follow-up of 47.4 (range 43.9-49.2) months, investigator-assessed ORR was 50% (95% CI 36% to 65%) and disease control rate was 70% (95% CI 55% to 82%). The median time to response per investigator was 2.8 (range 1.3-33.1) months, and median duration of response was 42.7 (range 2.8-47.0+) months. The median progression-free survival per investigator was 27.5 (95% CI 5.3 to 43.7) months with a progression-free survival rate at 3 years of 38%, and median overall survival was not reached (95% CI 17.2 months to not estimable), with a 56% overall survival rate at 3 years. The most common any-grade treatment-related adverse events (TRAEs) were diarrhea (24%), asthenia (16%), and hypothyroidism (12%). Grade 3 or 4 TRAEs were reported in 14% of patients, and TRAEs of any grade leading to discontinuation were observed in 8% of patients. No treatment-related deaths were reported.<h4>Conclusions</h4>Nivolumab plus relatlimab provided durable clinical benefit and was well tolerated in previously treated patients with MSI-H/dMMR metastatic CRC.<h4>Trial registration number</h4>NCT02060188."],"journal":["Journal for immunotherapy of cancer"],"pubmed_title":["Nivolumab plus relatlimab in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase II CheckMate 142 study."],"pmcid":["PMC11149130"],"funding_grant_id":["n/a"],"pubmed_authors":["Aglietta M","Garcia-Alfonso P","McCraith SM","Lei M","Limon Miron ML","Cubillo Gracian A","El-Rayes B","Lonardi S","Overman MJ","Gelsomino F","Hill AG","Van Cutsem E","Wong M","He B","Leonard G"],"additional_accession":[]},"is_claimable":false,"name":"Nivolumab plus relatlimab in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase II CheckMate 142 study.","description":"<h4>Background</h4>Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma. Here, we present the results from patients with MSI-H/dMMR metastatic CRC treated with nivolumab plus relatlimab in the CheckMate 142 study.<h4>Methods</h4>In this open-label, phase II study, previously treated patients with MSI-H/dMMR metastatic CRC received nivolumab 240 mg plus relatlimab 160 mg intravenously every 2 weeks. The primary end point was investigator-assessed objective response rate (ORR).<h4>Results</h4>A total of 50 previously treated patients received nivolumab plus relatlimab. With median follow-up of 47.4 (range 43.9-49.2) months, investigator-assessed ORR was 50% (95% CI 36% to 65%) and disease control rate was 70% (95% CI 55% to 82%). The median time to response per investigator was 2.8 (range 1.3-33.1) months, and median duration of response was 42.7 (range 2.8-47.0+) months. The median progression-free survival per investigator was 27.5 (95% CI 5.3 to 43.7) months with a progression-free survival rate at 3 years of 38%, and median overall survival was not reached (95% CI 17.2 months to not estimable), with a 56% overall survival rate at 3 years. The most common any-grade treatment-related adverse events (TRAEs) were diarrhea (24%), asthenia (16%), and hypothyroidism (12%). Grade 3 or 4 TRAEs were reported in 14% of patients, and TRAEs of any grade leading to discontinuation were observed in 8% of patients. No treatment-related deaths were reported.<h4>Conclusions</h4>Nivolumab plus relatlimab provided durable clinical benefit and was well tolerated in previously treated patients with MSI-H/dMMR metastatic CRC.<h4>Trial registration number</h4>NCT02060188.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-17T06:35:43.125Z","creation":"2026-06-17T03:06:57.154Z"},"accession":"S-EPMC11149130","cross_references":{"pubmed":["38821718"],"doi":["10.1136/jitc-2023-008689"]}}