I presented results on the expanded phase I trial of botensilimab and balstilimab in metastatic pretreated microsatellite stable colorectal cancer. Botensilimab is a novel multifunctional anti-CTLA-4 and balstilimab is an anti-PD-1 antibody. 

What did you do?

This was an expansion cohort of a phase I trial so in total 101 microsatellite stable colorectal cancer patients were enrolled in this study. 87 patients had received at least one of their on-study imaging assessments and were evaluable for the efficacy outcomes.

What were the findings?

Among the 87 efficacy evaluable patients, 18% had confirmed objective responses. This translated into a 12-month overall survival estimate of 62% in the total population. We also distinguished between patients who did and did not have active liver metastases as a predictive biomarker. Patients without active liver metastases were those defined as never having had liver metastases or those who had had a prior history of liver metastases but they had been effectively resected or ablated. Among that population the objective response rate was 23% and the disease control rate 80%.

Median overall survival among the entire population was 20.9 months. That was comparable in the overall population as well as the efficacy evaluable population. Again, in those who did not have active liver metastases the follow-up was still ongoing in the majority of patients, but the 12-month survival estimate was 74%. 

What adverse events did you see?

The majority of the adverse events were grade 1 and 2; there were no treatment-related deaths and no new safety signals compared to when these agents have been evaluated in other disease cohorts and in prior presentations. The main toxicity that we have seen is immune mediated diarrhoea and colitis. That was the most common and it occurred in 40% of subjects. Among those, 16% experienced a grade 3 and 1% a grade 4. Importantly, this toxicity was reversible and we are learning more that with early intervention we are able to reverse the immune-mediated diarrhoea and colitis. 

Also, different from what we’ve seen with other immune therapies, there was little visceral toxicity outside of the GI tract. 

What are the implications and what’s next?

We found these results really encouraging in that we are seeing activity in cold or immune oncology refractory tumours. Botensilimab is the first immune therapy agent that has shown a signal of activity in microsatellite stable, or what were thought to be cold, immune-refractory colorectal cancer. Patients continue to experience response and durable responses and we are seeing incremental survival benefits compared to what we have seen with historical data of other targeted and cytotoxic agents that are approved in this population.

Moving forward, a randomised global phase II trial is currently enrolling patients with refractory microsatellite stable colorectal cancer who do not have active liver metastases. We are excited to see what comes of that study and those results.

For patients with refractory microsatellite stable colorectal cancer, standard of care options really offer very modest benefit and clearly new therapies are needed. We are encouraged by the early phase results of this immune therapy combination in this population. 

Lastly, I just want to thank the patients and their families and support networks who participated in this trial and supporting this effort.