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

Combining Capecitabine/Oxaliplatin Chemotherapy With Cemiplimab Alone or in Combination With Fianlimab or REGN7075 for the Neoadjuvant Treatment of Locally Advanced Rectal Cancer

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Cemiplimab; Drug: Fianlimab; Drug: REGN7075

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
      • Principal Investigator: Eric Christenson, MD
      • Contact: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
  • cT3 node-positive
  • T: Tumor has grown through the muscularis propria into the serosa but has not invaded nearby organs
  • N: At least 1 perirectal lymph node ≥ 5 mm and no more than 4 perirectal lymph nodes > 10 mm in size in short axis
  • M: No evidence of metastasis
• Absence of distant metastases on CT or MRI imaging
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures.
• LVEF assessment with documented LVEF ≥ 50% by either TTE or MUGA (TTE preferred) within 6 months from first study drug administration.
• For both Women and Men, must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• 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.
• Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.
• Patient is pregnant or breastfeeding.
• Unwilling or unable to follow the study schedule for any reason.
• Patient received a live vaccine within 30 days of planned start of study medication.
• Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication.
• Patients with T4 disease or N2 disease (as defined by >/= 4 lymph nodes, each greater or equal to 10 mm in short axis).
• Evidence that the tumor is adjacent to (defined as within 3 mm of) the mesorectal fascia on pre-operative MRI or endorectal ultrasound or pelvic CT scan.
• Patients with symptomatic untreated bowel obstruction due to rectal cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Oxaliplatin, Capecitabine, Cemiplimab)	Drug: Oxaliplatin; 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.; Drug: Capecitabine; 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.; Other Names: Xeloda; Drug: Cemiplimab; Patients will receive Cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN2810; LIBTAYO
Experimental: Arm B (Oxaliplatin, Capecitabine, Cemiplimab, Fianlimab)	Drug: Oxaliplatin; 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.; Drug: Capecitabine; 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.; Other Names: Xeloda; Drug: Cemiplimab; Patients will receive Cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN2810; LIBTAYO; Drug: Fianlimab; Patients will receive Fianlimab (1600 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN3767
Experimental: Arm C (Oxaliplatin, Capecitabine, Cemiplimab, REGN7075)	Drug: Oxaliplatin; 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.; Drug: Capecitabine; 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.; Other Names: Xeloda; Drug: Cemiplimab; Patients will receive Cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN2810; LIBTAYO; Drug: REGN7075; Patients will receive REGN7075 (2700 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks
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).	24 months
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.	24 months
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).	24 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Eric Christenson, MD, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Capecitabine; Carcinoma; Immunotherapy; Adenocarcinoma; Chemotherapy; Rectal Cancer; Oxaliplatin; CAPOX; Cemiplimab; Fianlimab; REGEN7075; Anti-PD-1 (Programmed Death-Ligand 1)(protein immune checkpoint); PD-L1 (Programmed Death-Ligand 1)(protein immune checkpoint)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Colonic Diseases; Rectal Neoplasms; Carcinoma; Colorectal Neoplasms; Adenocarcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; cemiplimab
• Other Study ID Numbers: J25118; IRB00505702 (Other Identifier: Johns Hopkins Medical Institution)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No