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

NCT ID: NCT07281768

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-03-31
• Study Completion Date: 2030-03-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (Oxaliplatin, Capecitabine, Cemiplimab)

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: 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.

Cemiplimab

Intervention Type: 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.

Arm B (Oxaliplatin, Capecitabine, Cemiplimab, Fianlimab)

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: 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.

Cemiplimab

Intervention Type: 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.

Fianlimab

Intervention Type: 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.

Arm C (Oxaliplatin, Capecitabine, Cemiplimab, REGN7075)

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: 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.

Cemiplimab

Intervention Type: 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.

REGN7075

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Xeloda; REGN2810; LIBTAYO; REGN3767

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Christenson, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Locations

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Countries

United States

Central Contacts

Colleen Apostol, RN

Role: CONTACT

GIClinicalTrials@jhmi.edu

410-614-3644

Facility Contacts

Colleen Apostol, RN

Role: primary

GIClinicalTrials@jhmi.edu

410-614-3644

Other Identifiers

IRB00505702

Identifier Type: OTHER

Identifier Source: secondary_id

J25118

Identifier Type: -

Identifier Source: org_study_id