A Single-arm Phase II Clinical Study of Camrelizumab Combined With Long-course Chemoradiotherapy for Total Neoadjuvant Therapy in Locally Advanced Low pMMR/MSS Rectal Cancer

A Single-arm Phase II Clinical Study of Camrelizumab Combined With Long-course Chemoradiotherapy for Total Neoadjuvant Therapy in Locally Advanced Low pMMR/MSS Rectal Cancer

In pMMR/MSS locally advanced rectal cancer, can the innovative "chemo-immunotherapy induction + LCRT + chemo-immunotherapy consolidation" approach significantly improve the complete response rate and create opportunities for organ preservation?

Inclusion Criteria:

• Aged 18-75 years, male or female;

Histologically confirmed T3-4 and/or N+ rectal adenocarcinoma (AJCC/UICC TNM staging, 8th edition);

Lower margin of the tumor ≤10 cm from the anal verge;

Expected to achieve R0 resection;

Eastern Cooperative Oncology Group (ECOG) performance status 0-1;

Able to swallow tablets normally;

No prior anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc.;

Planned to undergo surgical treatment after neoadjuvant therapy;

No contraindications to surgery;

Laboratory tests must meet the following requirements: white blood cell count (WBC) ≥4×10⁹/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; hemoglobin ≥90 g/L; serum total bilirubin ≤1.5× upper limit of normal (ULN); serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN; serum creatinine ≤1.5× ULN or creatinine clearance ≥50 mL/min; international normalized ratio (INR) ≤1.5× ULN; activated partial thromboplastin time (APTT) ≤1.5× ULN;

Fertile male or female patients willing to use contraceptive measures during the trial.

Exclusion Criteria:

• Prior or current receipt of any anti-tumor therapy for cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.

Known genetic testing showing MSI-H (microsatellite instability-high) or immunohistochemistry showing dMMR (deficient mismatch repair).

Major surgery or severe trauma within 4 weeks prior to the first dose of study drug.

Known allergy, hypersensitivity, or contraindication to any component of camrelizumab or platinum-based agents.

Presence of poorly controlled cardiac clinical symptoms or diseases, including but not limited to: (1) heart failure ≥ NYHA class II; (2) unstable angina; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular or ventricular arrhythmias that have not been clinically intervened or remain poorly controlled after intervention.

Severe infection (CTCAE grade >2) within 4 weeks prior to the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; baseline chest imaging indicating active pulmonary inflammation; presence of signs or symptoms of infection within 14 days prior to the first dose of study drug, or requiring oral or intravenous antibiotic therapy (excluding prophylactic antibiotic use).

Presence of any active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism [excluding patients with stable hormone levels after treatment]; patients with childhood asthma that has completely resolved and requires no intervention in adulthood, or vitiligo, may be included; subjects requiring bronchodilators for medical intervention are not eligible).

Congenital or acquired immunodeficiency, such as HIV infection, active hepatitis B (HBV DNA ≥500 IU/mL), hepatitis C (positive HCV antibody with HCV-RNA above the lower limit of detection of the assay), or co-infection with hepatitis B and C.

Use of immunosuppressive drugs within 14 days prior to the first dose of study drug, excluding nasal and inhaled corticosteroids or physiological doses of systemic corticosteroids (i.e., no more than 10 mg/day prednisone or equivalent physiological dose of other corticosteroids).

Known interstitial lung disease, except for interstitial changes detected only on imaging.

Diagnosis of another malignancy within 5 years prior to the first dose of study drug, except for malignancies with a low risk of metastasis or death (5-year survival rate >90%), such as adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ, which may be considered for enrollment.

Pregnant or breastfeeding women.

Any other factors deemed by the investigator that may lead to premature termination of the study, such as other serious diseases (including psychiatric disorders) requiring concomitant treatment, alcoholism, drug abuse, family or social factors, or factors that may affect subject safety or compliance.