Neoadjuvant Botensilimab/Balstilimab for localized mismatch repair proficient and deficient colon cancer: Results of the NEST phase 2 clinical trial.

Authors

Manish A Shah, Erika Hissong, Mehraneh D Jafari, Pashtoon Murtaza Kasi, Maider Astorkia, Sahrish Khan, Casey Owens, Zhengming Chen, Heather Yeo, Fabio Socciarelli, Sandipto Sarkar, Alana Nguyen, Despina Siolas, Allyson Ocean, Kelly Garrett, Lea Lowenfeld, Alessio Pigazzi, Preethi Guniganti, Sanjay Patel, Doron Betel, Manuel Hidalgo

Published in

Clinical cancer research : an official journal of the American Association for Cancer Research. Aug 26, 2026. Epub Aug 26, 2026.

Abstract

Effective immunotherapy for mismatch repair proficient colorectal cancer (CRC) is lacking. We examined the safety and efficacy of the novel next-generation immune activator/Fc-enhanced CTLA-4 inhibitor botensilimab (BOT) plus PD-1 inhibitor balstilimab (BAL) in the neoadjuvant setting for patients with resectable CRC.
Patients 18 years of age or older with non-metastatic CRC awaiting surgical resection were eligible. BOT/BAL was administered followed by surgical resection. In cohort A, patients received BOT 75 mg d1 and BAL 240 mg d1, 15; in cohorts B/C, patients received 2 additional BAL doses (d29, 43). The primary study objectives were safety, feasibility (based on surgery delay), and pathologic response. Exploratory analyses examined changes in the tumor microenvironment.
Twenty-four eligible patients (26 tumors, n=22 pMMR; n=4 dMMR) were enrolled (two patients had synchronous primary tumors). Neoadjuvant BOT/BAL was safe and did not delay planned surgery in any patient. The major pathologic response rate was 41% (95% CI, 21%-64%) for pMMR, and 100% (95% CI, 40%-100%) for dMMR CRC. BOT/BAL was associated with significant anti-tumor effects in the tumor microenvironment, with an increase in the density and proportion of CD8+ T cells, a reduction in tumor infiltrating FOXP3+ Tregs, and evidence of increased immune cell-cell interaction in responding patients.
These findings demonstrate safety, feasibility, and encouraging pathological responses for BOT/BAL in both non-metastatic pMMR and dMMR CRC. Tumor microenvironment remodeling suggests a robust anti-tumor immune response induced by immunotherapy. These data support the continued development of BOT/BAL in CRC.

PMID:
42644724
Bibliographic data and abstract were imported from PubMed on 26 Aug 2026.

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