Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer.
Pashtoon Murtaza KasiManuel HildagoMehraneh D JafariHeather YeoLea LowenfeldUqba KhanAlana T H NguyenDespina SiolasBrandon SwedJini HyunSahrish KhanMadeleine WoodBenjamin SamsteinJuan P RoccaAllyson J OceanElizabeta C PopaDaniel H HuntNikhil P UppalKelly A GarrettAlessio PigazziXi Kathy ZhouManish A ShahErika HissongPublished in: Oncogene (2023)
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.
Keyphrases
- rectal cancer
- locally advanced
- immune response
- neoadjuvant chemotherapy
- advanced cancer
- phase ii study
- clinical trial
- squamous cell carcinoma
- palliative care
- end stage renal disease
- radiation therapy
- newly diagnosed
- chronic kidney disease
- lymph node
- prognostic factors
- high throughput
- gene expression
- peritoneal dialysis
- genome wide
- open label
- robot assisted
- dendritic cells
- toll like receptor
- study protocol
- dna methylation
- phase ii
- drug induced
- patient reported
- minimally invasive
- double blind