Capecitabine/Oxaliplatin chemo with cemiplimab with or without fianlimab or REGN7075 for locally advanced rectal cancer
Official title: Combining Capecitabine/Oxaliplatin Chemotherapy With Cemiplimab Alone or in Combination With Fianlimab or REGN7075 for the Neoadjuvant Treatment of Locally Advanced Rectal Cancer
Run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · NCT07281768 · Data updated 2026-11-12
This trial tests whether adding cemiplimab, cemiplimab with fianlimab, or cemiplimab with REGN7075 to CAPOX can help people with MSS locally advanced rectal cancer before surgery.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 66 (estimated) |
| Sponsor | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Academic / other |
| Drugs / interventions | radiation, cemiplimab, fianlimab |
| Locations | 1 site (Baltimore, Maryland) |
| Status | Recruiting |
| Started | July 14, 2026 |
| Main results expected | July 2030 |
| Study ends | July 2030 |
| Registry record updated | July 21, 2026 |
| Trial ID | NCT07281768 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults with MSS/pMMR rectal adenocarcinoma, ECOG 0-1, no prior systemic therapy or radiation, and a plan for sphincter-sparing surgery after neoadjuvant treatment.
✕Probably not a fit
Patients with non-MSS tumors, higher disease burden not amenable to sphincter-sparing surgery, or intolerance to CAPOX or immunotherapy may not benefit.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase 2 trial investigates neoadjuvant CAPOX chemotherapy combined with immune therapies in patients with microsatellite stable locally advanced rectal cancer. Participants receive one of three antibody combinations with capecitabine and oxaliplatin to assess safety and clinical activity prior to planned sphincter-sparing surgery. Eligible patients have MSS/pMMR rectal adenocarcinoma, ECOG 0-1, and no prior systemic therapy or radiation. The study is led by Johns Hopkins with Regeneron as a collaborator and is conducted at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore. Primary goals focus on safety and signals of tumor response to the combination regimens.
Why it matters
Potential benefit: If successful, the approach could improve tumor response and increase the likelihood of sphincter-sparing surgery for locally advanced rectal cancer.
How similar studies have gone: Previous studies combining chemo with immunotherapy in colorectal cancer have shown potential activity, but results vary and this specific combination in MSS locally advanced rectal cancer is exploratory.
Who can join: the full rules
Show full inclusion / exclusion 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.
Where it's running
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Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States Recruiting
Study contacts
- Principal investigator: Eric Christenson, MD — Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
- Study coordinator: Colleen Apostol, RN
- Email: GIClinicalTrials@jhmi.edu
- Phone: 410-614-3644
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.