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Combination botensilimab plus balstilimab demonstrates promising activity in heavily pre-treated MSS CRC

Presented by
Prof. Anthony El-Khoueiry, Norris Comprehensive Cancer Center, CA, USA
ASCO GI 2023
Phase 1, C-800
The combination therapy of botensilimab plus balstilimab resulted in encouraging anti-tumour activity in heavily pre-treated patients with microsatellite stable colorectal cancer (MSS CRC) in a phase 1a/1b trial. According to the authors, the safety profile of this treatment regimen was manageable.

“Botensilimab is an Fc-enhanced CTLA-4 inhibitor, which displayed activity in ‘cold’ and immunotherapy-refractory tumours,” said Prof. Anthony El-Khoueiry (Norris Comprehensive Cancer Center, CA, USA) [1]. The phase 1a/1b C-800 study (NCT03860272) is the first in-human trial to combine botensilimab plus balstilimab (a PD-1 antagonist) in patients with advanced cancer [2]. In total, 70 patients with refractory metastatic MSS CRC received 1 or 2 mg/kg of botensilimab, every 6 weeks, and 3 mg/kg of the PD-1 inhibitor, every 2 weeks. Patients had received a median of 4 prior lines of therapy.

The overall response rate was 23%, mostly comprised by partial responses (21%; see Figure). In addition, the stable disease rate was 53%, resulting in a disease control rate of 76%. The median progression-free survival was 4.1 months and the median overall survival (OS) had not been reached at the time of the presentation. In patients with active liver metastases the 12-month OS-rate was 40%, whereas the corresponding rate in patients without active liver metastases was 81%.

Figure: Deep objective responses with botensilimab plus balstilimab [2]

According to Prof. El-Khoueiry, the safety profile of the combination therapy was manageable. Any grade treatment-related adverse events were seen in 91% of the patients and grade 3 or 4 events were observed in 40% and 3% of the patients, respectively. Immune-mediated diarrhoea and colitis was the most common grade 3 adverse event, occurring in 20% of the participants.

The promising anti-tumour activity and manageable safety profile of the combination therapy of botensilimab and balstilimab in this phase 1a/1b trial has instigated further investigation of this regimen. A randomised, phase 2 trial in MSS CRC patients is enrolling (NCT05608044) and a global, phase 3 trial is planned.

  1. Waight JD, et al. Cancer Cell. 2018;33(6):1033–1047.
  2. El-Khoueiry AB, et al. Results from a phase 1a/1b study of botensilimab (BOT), a novel innate/adaptive immune activator, plus balstilimab (BAL; anti-PD-1 antibody) in metastatic heavily pretreated microsatellite stable colorectal cancer (MSS CRC). Late-breaking abstract 8, ASCO GI 2023, 19–21 January, San Francisco, CA, USA.

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