Author: By Lynda Williams,s medwireNews Reporter
medwireNews: Botensilimab plus balstilimab may offer a novel treatment regimen for patients with metastatic colorectal cancer (CRC) who have microsatellite stable (MSS) disease, delegates were told at the ESMO World Congress on Gastrointestinal Cancer 2022 in Barcelona, Spain.
The C-800 study results were presented by Anthony El-Khoueiry, from the University of Southern California in Los Angeles, USA, who said that the combination of second-generation CTLA-4 inhibitor and PD-1 inhibitor has achieved “durable objective responses and prolonged stable disease in heavily pretreated patients with MSS CRC”.
He explained that botensilimab is a Fc-enhanced CTLA-4 inhibitor designed “to treat cold and immuno-oncology refractory tumours” and that balstilimab is a PD-1 inhibitor that has “safety and efficacy comparable to currently approved” anti-PD-1 agents.
The first-in-human study of the combination included a phase Ib expansion cohort of 41 patients with metastatic MSS CRC (59% women, median age 57 years) who received botensilimab 1 or 2 mg/kg every 6 weeks plus balstilimab 3 mg/kg every 2 weeks for up to 2 years.
The participants had previously received a median of four treatments, including prior immunotherapy in 34% of cases; 49% of patients had a RAS mutation and 2% a BRAF mutation.
After a median follow-up of 5.8 months, 24% of patients had achieved an objective response, and the disease control rate was 73%, with responses ongoing in eight out of the 10 responders at time of analysis.
The researchers also examined the outcomes of the 24 participants with no history of liver metastases or whose liver metastases had been resected or ablated without recurrence. Among these patients, the objective response rate was 42% and the disease control rate was 96%.
Discussing the safety data for the study, Anthony El-Khoueiry said the combination was “well tolerated” after a median 2.8 months of treatment, noting that treatment-related adverse events (TRAEs) had occurred in 76% of patients at grade 1–3 but there were no grade 4 or 5 incidences.
The most common grade 3 TRAEs were diarrhoea and colitis in 10% of patients, with individual (2%) incidences of elevated aspartate aminotransferase, arthralgia, fatigue and pyrexia.
The presenter emphasized that there was no evidence of hypophysitis at any grade, “consistent with reduced complement binding of botensilimab”, and that both botensilimab and balstilimab were discontinued by 10% of patients.
He summarised that botensilimab plus balstilimab is the first immunotherapy-only regimen that has shown activity in patients with MSS CRC and may have an “enriched response rate” among individuals without active liver metastases.
“Biomarker and translational analyses are ongoing”, Anthony El-Khoueiry said, adding that a global phase II trial for patients with MSS CRC will launch in 2022.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group
Reference
- Bullock AJ, Grossman JE, Fakih MG, et al. Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer. Ann Oncol 2022; 33 (suppl 4): S376. doi: org/10.1016/j.annonc.2022.05.479
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group