학술논문
Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer.
Document Type
article
Author
Yeo, Heather; Lowenfeld, Lea; Khan, Uqba; Nguyen, Alana; Siolas, Despina; Swed, Brandon; Hyun, Jini; Khan, Sahrish; Wood, Madeleine; Samstein, Benjamin; Rocca, Juan; Ocean, Allyson; Popa, Elizabeta; Hunt, Daniel; Uppal, Nikhil; Garrett, Kelly; Pigazzi, Alessio; Zhou, Xi; Shah, Manish; Hissong, Erika; Kasi, Pashtoon; Hidalgo, Manuel; Jafari, Mehraneh
Source
Oncogene. 42(44)
Subject
Language
Abstract
In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed (inside-out (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.