Recruiting

Phase 2

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

Sponsor:

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Code:

NCT07281768

Conditions

Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Oxaliplatin

Capecitabine

Cemiplimab

Fianlimab

REGN7075

Study Details

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 ID

NCT07281768

Start date

Jul 14, 2026

Status verified date

Jul, 2026

Completion date

Jul, 2030

Anticipated

Primary completion date

Jul, 2030

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

66 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (Oxaliplatin, Capecitabine, Cemiplimab)

experimental: Arm B (Oxaliplatin, Capecitabine, Cemiplimab, Fianlimab)

experimental: Arm C (Oxaliplatin, Capecitabine, Cemiplimab, REGN7075)

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.

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.

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.

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.

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.

Primary outcome measure

Pathologic complete response (pCR) rate [ Time Frame: 24 months ]

Central Contacts and Locations

Central contacts

Colleen Apostol, RN

410-614-3644 GIClinicalTrials@jhmi.edu

Locations

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Colleen Apostol, RN

410-614-3644 GIClinicalTrials@jhmi.edu

Principal Investigator:

Eric Christenson, MD

More Information

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last update posted

Jul 21, 2026

Last verified

Jul, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins on 2026-07-21.