Capecitabine/Oxaliplatin Chemotherapy and Cemiplimab With or Without Fianlimab or REGN7075 in Locally Advanced Rectal Cancer

NCT07281768 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J25118IRB00505702
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Colorectal Cancer

Keywords

Rectal Cancer; Cemiplimab; Fianlimab; REGEN7075; Oxaliplatin; Capecitabine; Immunotherapy; Anti-PD-1 (Programmed Death-Ligand 1)(protein immune checkpoint); PD-L1 (Programmed Death-Ligand 1)(protein immune checkpoint); Adenocarcinoma; Carcinoma; CAPOX; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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).

  24 months

Secondary Outcomes (4)

• Number of participants experiencing grade 3 or above drug-related toxicities

  12 weeks

• Pathologic Response Rate

  24 months

• Event-free Survival (EFS)

  24 months

• Composite Complete Response Rate

  24 months

Study Arms (3)

Arm A (Oxaliplatin, Capecitabine, Cemiplimab)

EXPERIMENTAL

Drug: Oxaliplatin; Drug: Capecitabine; Drug: Cemiplimab

Arm B (Oxaliplatin, Capecitabine, Cemiplimab, Fianlimab)

EXPERIMENTAL

Drug: Oxaliplatin; Drug: Capecitabine; Drug: Cemiplimab; Drug: Fianlimab

Arm C (Oxaliplatin, Capecitabine, Cemiplimab, REGN7075)

EXPERIMENTAL

Drug: Oxaliplatin; Drug: Capecitabine; Drug: Cemiplimab; Drug: REGN7075

Interventions

Oxaliplatin DRUG

Patients will receive Oxaliplatin (130mg/m\^2 administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.

Arm A (Oxaliplatin, Capecitabine, Cemiplimab); Arm B (Oxaliplatin, Capecitabine, Cemiplimab, Fianlimab); Arm C (Oxaliplatin, Capecitabine, Cemiplimab, REGN7075)

Capecitabine DRUG

Patients 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.

Also known as: Xeloda

Arm A (Oxaliplatin, Capecitabine, Cemiplimab); Arm B (Oxaliplatin, Capecitabine, Cemiplimab, Fianlimab); Arm C (Oxaliplatin, Capecitabine, Cemiplimab, REGN7075)

Cemiplimab DRUG

Patients will receive Cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.

Also known as: REGN2810, LIBTAYO

Arm A (Oxaliplatin, Capecitabine, Cemiplimab); Arm B (Oxaliplatin, Capecitabine, Cemiplimab, Fianlimab); Arm C (Oxaliplatin, Capecitabine, Cemiplimab, REGN7075)

Fianlimab DRUG

Patients will receive Fianlimab (1600 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.

Also known as: REGN3767

Arm B (Oxaliplatin, Capecitabine, Cemiplimab, Fianlimab)

REGN7075 DRUG

Patients will receive REGN7075 (2700 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.

Arm C (Oxaliplatin, Capecitabine, Cemiplimab, REGN7075)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Must not have received any prior systemic treatment or radiation.
• Candidate for sphincter-sparing surgical resection after neoadjuvant therapy according to the primary surgeon.
• Patients have the following clinical staging:
• cT2 node-positive:
• T: Tumor is invading the muscularis propria but has not grown through it to the serosa
• N: At least 1 perirectal lymph node ≥5 mm and no more than 4 perirectal lymph nodes \>10 mm in short axis
• M: No evidence of metastasis
• cT3 node-negative
• T: Tumor has grown through the muscularis propria into the serosa but has not invaded nearby organs
• N: No perirectal lymph nodes ≥ 5 mm in size that suggest tumor involvement
• M: No evidence of metastasis

You may not qualify if:

• 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.
• Currently using any chronic systemic steroids.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• History of encephalitis, meningitis, dementia, Parkinson's or uncontrolled seizures within 1 year prior to the first dose of study drug.
• Uncontrolled infection of HIV, HBV, HCV, or Tuberculosis.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Active autoimmune disease.
• Any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft.
• Patient has a pulse oximetry of \<92% on room air.
• Patient is on supplemental home oxygen.
• Has clinically significant heart disease.
• Troponin T (TnT) or troponin I (TnI) \> 2x institutional ULN at baseline.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms; Adenocarcinoma; Carcinoma

Interventions

Oxaliplatin; Capecitabine; cemiplimab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Eric Christenson, MD

  Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostol, RN

CONTACT

410-614-3644; GIClinicalTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2025
• First Posted: December 15, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)