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The first immunotherapy signal in the 95 percent of bowel cancers that have always ignored it: an engineered CTLA-4 antibody plus a PD-1 antibody shrank tumours in 17 percent of 101 heavily treated patients.
Bullock, Schlechter, Fakih and colleagues report outcomes in 148 heavily pre-treated patients with microsatellite stable metastatic colorectal cancer (six from dose escalation, 142 from dose expansion) treated with botensilimab, an Fc-enhanced multifunctional anti-CTLA-4 antibody designed to extend therapy to poorly immunogenic tumours, plus balstilimab, an anti-PD-1 antibody. The primary endpoint was safety and tolerability; secondary endpoints included investigator-assessed objective response, disease control, duration of response and progression-free survival. One hundred and one patients were response evaluable with at least six months of follow-up.
Treatment-related adverse events occurred in 131 of 148 patients (89 percent), most commonly fatigue (35 percent), diarrhoea (32 percent) and pyrexia (24 percent), with no grade 5 treatment-related events and a 12 percent discontinuation rate.
The first credible response signal in microsatellite stable colorectal cancer, and the reason the field's attention has moved to Fc engineering and to excluding patients with active liver metastases, in whom responses are rare.
Shares PD-1 blockade in tumors with mismatch-repair deficiency, No one can predict who responds to immunotherapy, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Heinz-Josef Lenz, CTLA-4, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares PD-1 blockade in tumors with mismatch-repair deficiency, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, PD-1 and the tag colorectal-evidence.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, PD-1, Immune checkpoint inhibitors and the tag colorectal-evidence.
Shares Heinz-Josef Lenz, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.
Shares Heinz-Josef Lenz, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.
Shares Heinz-Josef Lenz, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.