The purpose of this study is to evaluate the safety and clinical activity of combining cemiplimab, cemiplimab/fianlimab, or cemiplimab/REGN7075 with capecitabine/oxaliplatin (CAPOX) for the neoadjuvant treatment of patients with microsatellite stable (MSS) locally advanced rectal cancer (T2 node-positive, T3 node-negative, T3 node-positive).
Age ≥18 years.
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
Rectal cancer (with tumor tissue present at or below the peritoneal reflection) as determined by MRI pelvis or endoscopic ultrasound.
Have histologically proven mismatch repair proficient (pMMR) or microsatellite stable (MSS) rectal adenocarcinoma.
Have received an investigational agent or used an investigational device within 28 days of the first dose of study drug.
Have expected to require any other form of systemic or localized antineoplastic therapy while on study.
Have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.).
History of prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, or anti-Lag-3 antibodies for any reason.
Parallel
Oxaliplatin
DrugPatients will receive Oxaliplatin (130mg/m\^2 administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.
Capecitabine
DrugPatients will receive Capecitabine (1000mg/m\^2 administered orally) on Days 1 through 14 of each 21 day cycle for a total of 4 cycles of treatment.
Cemiplimab
DrugPatients will receive Cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.
Fianlimab
DrugPatients will receive Fianlimab (1600 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.
REGN7075
DrugPatients will receive REGN7075 (2700 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.
Pathologic complete response (pCR) rate
Proportion of subjects with a pathologic complete response (pCR) at the time of surgery. pCR is defined as subjects with no viable tumor cell noted on pathological evaluation of the resection specimen using the College of American Pathologists (CAP) tumor regression scoring system (CAP tumor regression score of 0).
Number of participants experiencing grade 3 or above drug-related toxicities
When calculating the incidence of Adverse Events (AEs), each AE (as defined by NCI CTCAE v6.0) will be counted only once for a given subject.
Pathologic Response Rate
Pathologic response rate as defined as the proportion of subjects with complete or partial tumor regression at the time of surgery using the College of American Pathologists (CAP) tumor regression scoring system (CAP tumor regression score of 0 to 2).
Event-free Survival (EFS)
EFS is defined as the number of months from the date of initiation of neoadjuvant treatment to disease relapse or development of metastatic disease (as assessed using RECIST 1.1 criteria) or death due to any cause. EFS will be censored at the date of the last scan for subjects without documentation of disease progression at the time of analysis.
Composite Complete Response Rate
Composite complete response rate is defined as the proportion of subjects with either a pathologic complete response (pCR) or those that remain disease-free for 24 months on radiographic imaging and endoscopic evaluation for those that elected to not go to surgery. pCR is defined as subjects with no viable tumor cell noted on pathological evaluation of the resection specimen using the College of American Pathologists (CAP) tumor regression scoring system (CAP tumor regression score of 0).
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
Regeneron Pharmaceuticals
Collaborator
