Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer
Author:
Kasi Pashtoon MurtazaORCID, Hidalgo ManuelORCID, Jafari Mehraneh D., Yeo Heather, Lowenfeld Lea, Khan Uqba, Nguyen Alana T. H., Siolas Despina, Swed Brandon, Hyun Jini, Khan Sahrish, Wood Madeleine, Samstein Benjamin, Rocca Juan P., Ocean Allyson J., Popa Elizabeta C., Hunt Daniel H., Uppal Nikhil P., Garrett Kelly A., Pigazzi Alessio, Zhou Xi KathyORCID, Shah Manish A.ORCID, Hissong Erika
Abstract
AbstractIn 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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Molecular Biology
Reference17 articles.
1. Le Saux O, Lounici Y, Wajda P, Barrin S, Caux C, Dubois B, et al. Neoadjuvant immune checkpoint inhibitors in cancer, current state of the art. Crit Rev Oncol Hematol. 2021;157:103172. 2. Marron TU, Galsky MD, Taouli B, Fiel MI, Ward S, Kim E, et al. Neoadjuvant clinical trials provide a window of opportunity for cancer drug discovery. Nat Med. 2022;28:626–9. 3. Chalabi M. The promise of neoadjuvant immunotherapy across solid tumors. 2023. https://meetings.asco.org/2023-asco-annual-meeting/15057?presentation=225720#225720 (Accessed 18 Aug 2023). 4. El-Khoueiry AB, Fakih M, Gordon MS, Tsimberidou AM, Bullock AJ, Wilky BA, 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). J Clin Oncol. 2023;41:LBA8. 5. Delepine C, Levey D, Krishnan S, Kim K-S, Sonabend A, Wilkens M, et al. 470 Botensilimab, an Fc-enhanced CTLA-4 antibody, enhances innate and adaptive immune activation to promote superior anti-tumor immunity in cold and I-O refractory tumors. J Immunother Cancer. 2022;10:A490.
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