Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: A phase 1 trial Journal Article
| Authors: | Bullock, A. J.; Schlechter, B. L.; Fakih, M. G.; Tsimberidou, A. M.; Grossman, J. E.; Gordon, M. S.; Wilky, B. A.; Pimentel, A.; Mahadevan, D.; Balmanoukian, A. S.; Sanborn, R. E.; Schwartz, G. K.; Abou-Alfa, G. K.; Segal, N. H.; Bockorny, B.; Moser, J. C.; Sharma, S.; Patel, J. M.; Wu, W.; Chand, D.; Rosenthal, K.; Mednick, G.; Delepine, C.; Curiel, T. J.; Stebbing, J.; Lenz, H. J.; O’Day, S. J.; El-Khoueiry, A. B. |
| Article Title: | Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: A phase 1 trial |
| Abstract: | Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study. The primary endpoint is safety and tolerability, which was evaluated separately in the dose-escalation portion of the study and in patients with MSS mCRC (using combined dose-escalation/dose-expansion data). Secondary endpoints include investigator-assessed RECIST version 1.1–confirmed objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS). Here we present outcomes in 148 heavily pre-treated patients with MSS mCRC (six from the dose-escalation cohort; 142 from the dose-expansion cohort) treated with BOT and BAL, 101 of whom were considered response evaluable with at least 6 months of follow-up. Treatment-related adverse events (TRAEs) occurred in 89% of patients with MSS mCRC (131/148), most commonly fatigue (35%, 52/148), diarrhea (32%, 47/148) and pyrexia (24%, 36/148), with no grade 5 TRAEs reported and a 12% discontinuation rate due to a TRAE (18/148; data fully mature). In the response-evaluable population (n = 101), ORR was 17% (17/101; 95% confidence interval (CI), 10–26%), and DCR was 61% (62/101; 95% CI, 51–71%). Median DOR was not reached (NR; 95% CI, 5.7 months–NR), and median PFS was 3.5 months (95% CI, 2.7–4.1 months), at a median follow-up of 10.3 months (range, 0.5–42.6 months; data continuing to mature). The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with durable responses. ClinicalTrials.gov identifier: NCT03860272. © The Author(s) 2024. |
| Keywords: | adult; treatment response; aged; aged, 80 and over; middle aged; unclassified drug; major clinical study; genetics; clinical trial; fatigue; cancer recurrence; hepatitis; bevacizumab; diarrhea; drug efficacy; drug safety; drug withdrawal; monotherapy; side effect; cancer patient; follow up; antineoplastic agent; cytotoxic t lymphocyte antigen 4 antibody; metastasis; progression free survival; neoplasm recurrence, local; gene expression profiling; anemia; nausea; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; cohort analysis; creatinine; steroid; creatinine blood level; drug effect; pathology; microsatellite dna; monoclonal antibody; arthralgia; chill; dizziness; dyspnea; fever; pneumonia; pruritus; rash; colorectal neoplasms; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; acute kidney failure; maculopapular rash; multicenter study; colorectal tumor; tumor recurrence; microsatellite instability; neoplasm metastasis; xerostomia; colitis; open study; creatine kinase; alkaline phosphatase blood level; phase 1 clinical trial; hypothyroidism; cancer control; drug therapy; drug dose increase; immunopathology; microsatellite repeats; creatine kinase blood level; hyperhidrosis; enterocolitis; steroid therapy; adrenal insufficiency; decreased appetite; metastatic colorectal cancer; hypophysitis; infliximab; overall response rate; myocarditis; refractory cancer; antibodies, monoclonal, humanized; combination drug therapy; regorafenib; very elderly; humans; human; male; female; article; patient history of radiotherapy; patient history of therapy; immune-mediated myocarditis; alanine aminotransferase level; aspartate aminotransferase level; tipiracil plus trifluridine; treatment response time; immune mediated enterocolitis; balstilimab; botensilimab; bevacizumab plus tipiracil plus trifluridine; immune-mediated hepatitis; immune-mediated hypophysitis; immune-mediated pneumonitis; microsatellite stable metastatic colorectal cancer |
| Journal Title: | Nature Medicine |
| Volume: | 30 |
| Issue: | 9 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-09-01 |
| Start Page: | 2558 |
| End Page: | 2567 |
| Language: | English |
| DOI: | 10.1038/s41591-024-03083-7 |
| PUBMED: | 38871975 |
| PROVIDER: | scopus |
| PMCID: | PMC11405281 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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