SHR-1701 with short-course radiotherapy and CAPOX before surgery for locally advanced rectal cancer

A Phase II, Prospective, Single Arm Study of Neoadjuvant SHR-1701 Combine With Chemoradiotherapy for Locally Advanced Rectal Cancer

This will test whether adding the drug SHR-1701 to short-course radiotherapy plus CAPOX before surgery helps people with locally advanced rectal cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT07478731 on ClinicalTrials.gov

What this trial studies

This Phase 2 neoadjuvant regimen gives one induction cycle of SHR-1701 plus CAPOX, then short-course radiotherapy (25 Gy in 5 fractions), followed by five consolidation cycles of SHR-1701 plus CAPOX before planned total mesorectal excision. SHR-1701 is given IV at a fixed dose every three weeks while CAPOX consists of oxaliplatin IV on Day 1 and oral capecitabine twice daily for 14 days of a 21-day cycle. Surgery (TME) is scheduled about 4–8 weeks after completing consolidation to allow tumor regression and recovery. Eligible patients are adults 18–75 with pathologically confirmed locally advanced rectal adenocarcinoma (e.g., cT3-4, cN2, EMVI+ or MRF+), pMMR or MSS/MSI-L status, ECOG 0–1, and no prior anti-tumor therapy.

Who should consider this trial

Good fit: Adults 18–75 with newly diagnosed, locally advanced rectal adenocarcinoma (cT3-4, cN2, EMVI+ or MRF+), pMMR or MSS/MSI-L, ECOG 0–1, able to swallow oral medication and planned for total mesorectal excision after neoadjuvant therapy.

Not a fit: Patients with metastatic disease, dMMR/MSI-H tumors, significant organ dysfunction, ECOG >1, prior anti-tumor therapy, or inability to tolerate CAPOX, SCRT, or surgery are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this approach could increase tumor shrinkage before surgery and raise rates of complete tumor removal and pathologic complete response, potentially improving long-term outcomes.

How similar studies have performed: Early-phase studies combining PD-1/PD-L1 agents with chemoradiation in rectal cancer have shown promising signals in some patients but remain unproven in pMMR/MSS disease, and SHR-1701 combinations are still investigational.

Eligibility criteria

Inclusion Criteria:

* 1: Sign the informed consent form and voluntarily participate in this study

  2: Age 18-75

  3: Pathologically confirmed rectal adenocarcinoma（At least meet any of the following criteria：cT3-4、cN2、EMVI+、MRF+）

  4: pMMR or MSS/MSI-L rectal adenocarcinoma

  5: The distance from tumor edge to the anal verge

  6: Expect to complete R0 resection

  7: Patients can swallow pills

  8: ECOG PS 0-1

  9: Patients has not received any anti-tumor treatment before, including surgery, radiotherapy, chemotherapy, targeting therapy and immunotherapy

  10: Plan to complete surgery after neoadjuvant therapy

  11: There is contraindication to surgery

  12: Main organ function efficient, including blood routine examination, blood biochemical examination, coagulation function

  13: Female subjects with reproductive capacity are required to undergo a serum pregnancy test 72 hours before starting the administration of the test drug, and the result must be negative. During the trial period and for at least 3 months after the last administration, they must take effective contraceptive measures (such as intrauterine devices, contraceptives, or condoms). For male subjects whose partners are female with reproductive capacity, effective contraceptive measures must be taken during the trial period and for at least 3 months after the last administration.

Exclusion Criteria:

1. Allergy to monoclonal antibody, SHR-1701, capecitabine, oxaliplatin and other platinum drugs
2. The patient previously received or is receiving any following treatments: a) Any surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc; b) Within 2 weeks before the first use of the study drug, is using immunosuppressive drugs or systemic hormone drugs to achieve immunosuppression (dose \> 10mg/day prednisone or equivalent); in the absence of active autoimmune diseases, inhalation or local use of steroids and doses \> 10mg/day prednisone or equivalent adrenal cortical hormones are allowed; c) Has received attenuated live vaccines within 4 weeks before the first use of the study drug; d) Has undergone major surgery or suffered severe trauma within 4 weeks prior to the first use of the study drug.
3. Having any active autoimmune disease or a history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism (considered for inclusion after hormone replacement therapy); patients with psoriasis or childhood asthma/allergy that has completely resolved and does not require any intervention after adulthood can be considered for inclusion, but patients who require medical intervention with bronchodilators cannot be included.
4. Have a history of immunodeficiency, including a positive HIV test result, or suffer from other acquired or congenital immune deficiency diseases, or have a history of organ transplantation or allogeneic bone marrow transplantation.
5. There are heart diseases or clinical symptoms that are not well controlled, including but not limited to: (1) NYHA grade II or above heart failure, (2) unstable angina pectoris, (3) having experienced myocardial infarction within the past year, (4) having clinically significant supraventricular or ventricular arrhythmias that have not been controlled through clinical intervention or remain poorly controlled even after clinical intervention.
6. Within 4 weeks prior to the first use of the study drug, there was a severe infection (CTCAE \> grade 2), such as severe pneumonia, bacteremia, infection complications, etc required hospitalization; those with baseline chest imaging indicating active pulmonary inflammation, those who had symptoms and signs of infection or required oral or intravenous antibiotic treatment within 14 days prior to the first use of the study drug, excluding cases where antibiotics were used prophylactically.
7. Those who were found to have active tuberculosis infection through medical history or CT examination, or those who had a history of active tuberculosis infection within the previous 1 year of enrollment, or those who had a history of active tuberculosis infection more than 1 year ago but did not receive proper treatment.
8. There is active hepatitis B (with HBVDNA ≥ 2000 IU/mL or 104 copies/mL) and hepatitis C (with positive hepatitis C antibody and HCVRNA above the detection limit of the analytical method)
9. If within the 5 years prior to the first use of the investigational drug, one has been diagnosed with any other malignant tumor, except for those with low risk of metastasis or mortality (with a 5-year survival rate \> 90%), such as fully treated skin basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ, etc., they may be considered for inclusion.
10. Pregnant or lactating women
11. Based on the researchers' assessment, there are other factors that could potentially lead to the premature termination of the study. These include having other serious illnesses (including mental disorders) that require combined treatment, alcohol abuse, drug abuse, family or social factors, which may affect the safety or compliance of the participants.

Where this trial is running

Wuhan, Hubei

• Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Qiu Hong

Conditions CRC