{ "abstract": "Purpose:: Microsatellite-stable metastatic colorectal cancer (MSS mCRC) has limited treatment options and responds poorly to conventional immunotherapy. We report extended follow-up results from a fully enrolled, phase Ib cohort evaluating botensilimab [BOT; Fc-enhanced anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4)] plus balstilimab [BAL; anti–programmed cell death protein 1 (PD-1)] in patients with MSS mCRC and no active liver metastases (NLM).\n\nPatients and Methods:: Patients received BOT 1 or 2 mg/kg every 6 weeks plus BAL 3 mg/kg every 2 weeks up to 2 years or until progression or unacceptable toxicity. The primary objective was safety/tolerability. Efficacy endpoints included objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS); overall survival (OS) was exploratory. Patients with prior regorafenib, trifluridine/tipiracil ± bevacizumab, or fruquintinib (“late-line exposed”) were analyzed post hoc.\n\nResults:: As of December 13, 2025, 123 patients were treated [median follow-up, 20.2 months (range, 0.7–62.3)]. The median prior lines was 3 (range, 1–10; 67% had ≥3 prior lines). The most common treatment-related adverse events were diarrhea (39%; grade ≥3, 8%) and fatigue (37%; grade ≥3, 2%). The ORR was 21% [95% confidence interval (CI), 14–29]. The median DOR was not reached (NR; 95% CI, 7.3–NR), the median PFS was 4.0 months (95% CI, 2.8–4.1), and the median OS was 21.2 months [95% CI, 16.2–23.8; 36-month OS, 33% (95% CI, 24–43)]. Efficacy was consistent in late line–exposed patients [n = 37; ORR, 22% (95% CI, 10–38); median OS, 16.2 months (95% CI, 9.7–31.3)].\n\nConclusions:: BOT + BAL demonstrated durable responses, long-term survival, and manageable safety in previously treated MSS mCRC NLM, including in late line–exposed patients. These results support further evaluation.", "abstract_shown": true, "affiliations": [ "Dana-Farber Cancer Institute, Boston, Massachusetts.", "City of Hope Comprehensive Cancer Center, Duarte, California.", "University of Texas, MD Anderson Cancer Center, Houston, Texas.", "Beth Israel Deaconess Medical Center, Boston, Massachusetts.", "University of Miami, Sylvester Comprehensive Cancer Center, Miami, Florida.", "HonorHealth Research Institute, Scottsdale, Arizona.", "University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California.", "Memorial Sloan Kettering Cancer Center, New York, New York.", "Weill Cornell Medical College, New York, New York.", "Trinity College Dublin, Dublin, Ireland.", "Mount Sinai, Tisch Cancer Center, New York, New York.", "University of Colorado Cancer Center, Aurora, Colorado.", "The Royal Marsden Hospital, London, United Kingdom.", "Agenus Inc., Lexington, Massachusetts." ], "article_type": "research article", "arxiv": null, "author_total": 22, "authors": [ { "affs": [ 0 ], "name": "Benjamin L. Schlechter", "orcid": "0000-0002-1529-3278" }, { "affs": [ 1 ], "name": "Marwan G. Fakih", "orcid": "0000-0002-6554-5488" }, { "affs": [ 2 ], "name": "Apostolia M. Tsimberidou", "orcid": "0000-0003-2713-233X" }, { "affs": [ 3 ], "name": "Andrea J. Bullock", "orcid": "0000-0001-7143-0225" }, { "affs": [ 4 ], "name": "Agustin Pimentel", "orcid": "0009-0000-2837-9049" }, { "affs": [ 5 ], "name": "Sunil Sharma", "orcid": "0000-0002-1308-5985" }, { "affs": [ 6 ], "name": "Heinz-Josef Lenz", "orcid": "0000-0003-2178-9568" }, { "affs": [ 5 ], "name": "Michael S. Gordon", "orcid": "0000-0002-7679-9504" }, { "affs": [ 7, 8, 9 ], "name": "Ghassan K. Abou-Alfa", "orcid": "0000-0002-1522-8054" }, { "affs": [ 10 ], "name": "Thomas U. Marron", "orcid": "0000-0001-5903-8191" }, { "affs": [ 11 ], "name": "Robert W. Lentz", "orcid": "0000-0002-7207-8195" }, { "affs": [ 11 ], "name": "Wells Messersmith", "orcid": "0000-0003-2349-0885" }, { "affs": [ 12 ], "name": "Ian Chau", "orcid": "0000-0003-0286-8703" }, { "affs": [ 3 ], "name": "Bruno Bockorny", "orcid": "0000-0002-9162-1560" }, { "affs": [ 13 ], "name": "Dhan Chand", "orcid": "0009-0003-8124-4399" }, { "affs": [ 13 ], "name": "Manushak Avagyan", "orcid": "0000-0003-2207-3107" }, { "affs": [ 13 ], "name": "Wei Wu", "orcid": "0009-0002-7782-4780" }, { "affs": [ 13 ], "name": "Benny Johnson", "orcid": "0000-0002-6826-6687" }, { "affs": [ 13 ], "name": "Joseph E. Grossman", "orcid": "0000-0002-2130-2783" }, { "affs": [ 13 ], "name": "Steven J. O’Day", "orcid": "0009-0005-5345-5417" }, { "affs": [ 6 ], "name": "Anthony B. El-Khoueiry", "orcid": "0000-0002-9053-3841" }, { "affs": [ 7, 8 ], "name": "Neil H. Segal", "orcid": "0000-0002-3047-2303" } ], "bibtex": "https://research.draconitic.com/paper/9xkknpk413mq6.bib", "cited_by": 1, "doi": "10.1158/1078-0432.ccr-26-1610", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13725327/", "id": "9xkknpk413mq6", "issns": [ "1078-0432", "1557-3265" ], "landing_url": "https://doi.org/10.1158/1078-0432.ccr-26-1610", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Clinical Trial Results" ], [ "heading", "Clinical Trials: Immunotherapy" ], [ "heading", "Colorectal Cancer" ], [ "heading", "Combination Immunotherapy" ], [ "heading", "Gastrointestinal Cancers" ], [ "heading", "Immunotherapy" ], [ "heading", "Phase I clinical trials" ], [ "openalex", "2730|Cancer Immunotherapy and Biomarkers" ] ], "openalex": "W7204535243", "pdf_url": "https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-26-1610/3825589/ccr-26-1610.pdf", "pmcid": "PMC13725327", "pmid": "42663536", "published": "2026-08-28", "publisher": null, "ris": "https://research.draconitic.com/paper/9xkknpk413mq6.ris", "sources": [ { "first_seen": "2026-11-04T12:23:44Z", "native_id": "PMC13725327", "source": "pmc", "url": "https://doi.org/10.1158/1078-0432.ccr-26-1610" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers", "subfield": "oncology" } ], "title": "Extended Follow-up of Botensilimab plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer without Active Liver Metastases", "title_text": "Extended Follow-up of Botensilimab plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer without Active Liver Metastases", "type": "peer-reviewed", "updated_at": "2026-11-06T12:21:37Z", "url": "https://research.draconitic.com/paper/9xkknpk413mq6", "venue": "Clinical Cancer Research", "versions": [] }