Neoadjuvant SHR-1701 Plus Chemoradiotherapy for Locally Advanced Rectal Cancer

Official title

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

Overview

The goal of this clinical trial is to learn if SHR-1701 combine with chemoradiotherapy works to treat severe CRC. Participants will take: Induction: SHR-1701 combined with CAPOX for one cycle. Radiotherapy: Short-course radiotherapy (SCRT) (25Gy/5F). Consolidation: SHR-1701 combined with CAPOX for five cycles, after which the subjects undergo TME surgery.

Detailed description

1. Induction Phase SHR-1701: Intravenous infusion at a fixed dose of 30 mg/kg, depending on the protocol), administered on Day 1.

CAPOX Regimen:

Oxaliplatin: 130 mg/m², intravenous infusion on Day 1;

Capecitabine: 1000 mg/m², orally twice daily from Day 1 to Day 14, followed by 7 days of rest.

This phase consists of 1 cycle (each cycle is 21 days). 2. Radiotherapy

Short-course radiotherapy (SCRT) will be initiated shortly after the induction phase:

Total dose: 25 Gy delivered in 5 fractions of 5 Gy each, administered on 5 consecutive days . 3. Consolidation Phase

Following radiotherapy, participants will continue treatment with SHR-1701 combined with CAPOX:

SHR-1701: Same dose as induction, administered every 3 weeks (Day 1 of each cycle).

CAPOX: Same regimen as induction, administered every 3 weeks.

This phase consists of 5 cycles (each cycle is 21 days). 4. Surgery After completion of the consolidation phase, total mesorectal excision (TME) will be performed based on investigator assessment and surgical indications.

Surgery is typically scheduled within 4 to 8 weeks after completion of consolidation therapy to allow adequate tumor regression and patient recovery.

Interventions

• Drug SHR-1701 neoadjuvant
  Induction: SHR-1701 combined with CAPOX for one cycle. Radiotherapy: Short-course radiotherapy (SCRT) (25Gy/5F). Consolidation: SHR-1701 combined with CAPOX for five cycles, after which the subjects undergo TME surgery.

Primary outcome measures

• pCR [Time frame: At surgery (pathological assessment)]

Secondary outcome measures (2)

• cCR [Time frame: At completion of neoadjuvant therapy (prior to surgery)]
• OS [Time frame: From date of randomization until date of death due to any cause, assessed up to 2 years]

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

• Allergy to monoclonal antibody, SHR-1701, capecitabine, oxaliplatin and other platinum drugs
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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)
• 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.
• Pregnant or lactating women
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tongji Medical College, Huazhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT07478731 · MA-CRC-II-018

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗