Neoadjuvant combined immunotherapy also effective in MSS/pMRR CRC

Presented by

Dr Mehraneh Jafari, Weill Cornell Medical Center, NY, USA

Conference

ESMO GI 2024

Trial

Phase 2, NEST-1

Doi
https://doi.org/10.55788/8d599540

Neoadjuvant treatment with a combination immunotherapy of botensilimab/balstilimab is safe and active in both MSS/pMMR and MSI-H/dMRR resectable colorectal cancer (CRC), first results from the phase 2 NEST-1 trial demonstrated.

Previously, the phase 2 NICHE-2 trial (NCT03026140) demonstrated that neoadjuvant nivolumab/ipilimumab induced a high rate of major pathological complete response (pCR) in patients with locally advanced microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) CRC [1]. In contrast, microsatellite stable/proficient mismatch repair (MSS/pMMR) resectable CRC is currently considered non-responsive to immune checkpoint inhibitors. However, good responses were observed recently with neoadjuvant botensilimab (an anti-CTLA-4 antibody) and balstilimab (an anti-PD-1 antibody) in 2 patients with resectable MSS/pMMR CRC [2].

To further evaluate the efficacy of neoadjuvant botensilimab/balstilimab in MSS/pMMR resectable CRC, Dr Mehraneh Jafari (Weill Cornell Medical Center, NY, USA) and colleagues performed the phase 2 NEST-1 trial (NCT05571293) [3]. NEST-1 enrolled 20 participants with resectable, non-metastatic CRC; 10 participants received neoadjuvant treatment with 1 dose of botensilimab and 2 doses of balstilimab followed by surgery, 10 participants received neoadjuvant treatment with 1 dose of botensilimab and up to 4 doses of balstilimab followed by surgery. Median time to surgery was 29.5 days in cohort 1 and 57 days in cohort 2.

Only 3 participants had MSI-H/dMMR CRC. They all achieved a major pathological response (≥50% regression), as did 71% of the MSS/pMMR participants. A pCR was achieved by 2 MSI-H/dMMR participants and by 6 MSS/pMMR participants.

Based on these results, Dr Jafari concluded that “neoadjuvant botensilimab/balstilimab is a safe and active regimen in both MSS/pMMR and MSI-H/dMRR resectable CRC. Responses increased with more doses of balstilimab, in conjunction with a longer interval to surgery.”

Chalabi M, et al. N Engl J Med 2024;390:1949-1958.
Kasi PM, et al. Oncogene. 2023;42:3252-3259.
Kasi PM, et al. Neoadjuvant botensilimab (BOT) plus balstilimab (BAL) in resectable mismatch repair proficient and deficient colorectal cancer: NEST-1 clinical trial. Abstract 8MO, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

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