Neoadjuvant radiotherapy with toripalimab, liposomal irinotecan, and capecitabine for pMMR locally advanced low rectal cancer

Study on the Efficacy and Safety of Neoadjuvant Radiotherapy Combined With Toripalimab, Liposomal Irinotecan, and Capecitabine in the Treatment of pMMR Locally Advanced Rectal Adenocarcinoma With Low Rectal Involvement

This trial will test whether adding toripalimab, liposomal irinotecan, and capecitabine to radiation before surgery helps adults with pMMR locally advanced low rectal cancer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 59 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Affiliated Cancer Hospital of Shantou University Medical College (Academic / other)
• Drugs / interventions: chemotherapy, Tislelizumab
• Locations: 1 site (Shantou, Guangdong)
• Trial ID: NCT07104604 on ClinicalTrials.gov

What this trial studies

This is a phase 1, single-center trial enrolling adults 18–75 with biopsy-confirmed pMMR locally advanced mid–lower rectal adenocarcinoma and high-risk features. Participants receive neoadjuvant radiotherapy combined with the PD-1 inhibitor toripalimab plus liposomal irinotecan and capecitabine prior to planned surgery. The study focuses on safety, tolerability, and preliminary signs of anti-tumor activity including imaging and pathologic responses. Regular clinical visits, laboratory monitoring, and imaging will be used to follow toxicity and tumor response at the Affiliated Cancer Hospital of Shantou University Medical College.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 with ECOG 0–1, biopsy-confirmed pMMR locally advanced mid–lower rectal adenocarcinoma (lower edge ≤10 cm from the anus) with high-risk features, no distant metastasis, and adequate organ function.

Not a fit: Patients with distant metastases, poor organ function, ECOG >1, or tumors with deficient MMR (dMMR) are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could increase tumor shrinkage before surgery, potentially improving rates of complete response and enabling less extensive surgery.

How similar studies have performed: Early-phase work combining immunotherapy with chemoradiation has shown promise in some settings but robust benefit for pMMR rectal cancer remains unproven.

Eligibility criteria

Here is the updated format for the \*\*Eligibility Criteria\*\* with bullet points for each item:

Inclusion Criteria:

* Age: 18-75 years, no gender restriction
* ECOG score 0-1
* Biopsy-confirmed pMMR (proficient mismatch repair) localized advanced low rectal adenocarcinoma (tumor's lower edge ≤ 10 cm from the anus)
* Presence of the following high-risk factors: T3N+/T4/N2/EMVI+/MRF+/lateral lymph node metastasis/inability to undergo sphincter-preserving surgery
* Routine chest and abdominal CT scans showing no distant metastasis
* Bone marrow function: Neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count (PLT) ≥ 100 × 10\^9/L, hemoglobin (Hb) ≥ 70 g/L
* Liver function: ALT, AST ≤ 2.5 × ULN (upper limit of normal); total bilirubin ≤ 1.5 × ULN; serum albumin ≥ 3 g/dL
* Kidney function: Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance ≥ 60 ml/min (calculated using the Cockcroft-Gault formula)
* For females and patients with reproductive potential, a negative pregnancy test must be done within 72 hours before starting the treatment, and the patient must agree to avoid pregnancy during the study treatment and for 6 months after the treatment. For males with reproductive potential partners, the patient must agree to use adequate medically approved contraception during and for 90 days after the final study treatment
* Patients must agree to receive the study's neoadjuvant chemotherapy regimen and sign an informed consent form

Exclusion Criteria:

* Patients with a history of other malignancies within the past 5 years (except for cured and non-recurring cancers such as in situ carcinoma, basal cell carcinoma of the skin, etc.)
* Patients with active, uncontrolled bacterial, viral, or fungal infections requiring systemic treatment, defined by persistent signs/symptoms related to infection, which do not improve despite appropriate antibiotics, antiviral treatments, and/or other therapies
* Patients with uncontrolled systemic diseases, including unstable angina, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmia, history of severe pericardial disease, or other cardiovascular diseases; uncontrolled hypertension (defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg despite appropriate antihypertensive treatment), or a history of hypertensive crisis, hypertensive encephalopathy; uncontrolled diabetes (fasting blood glucose ≥ 10 mmol/L), etc.
* Patients known to be allergic or intolerant to the treatment drugs or excipients used in this study
* Any clinical indicators showing contraindications to chemotherapy and surgery
* Patients using strong inhibitors or inducers of enzymes such as CYP3A4, CYP2C8, and UGT1A1
* Pregnant or breastfeeding women, and female patients of reproductive potential who refuse to use appropriate contraceptive measures during the study
* Patients who participated in other clinical trials within 4 weeks before enrollment
* Patients whom the investigator deems unsuitable for participation in the study

Where this trial is running

Shantou, Guangdong

• Shantou University Medical College Cancer Hospital — Shantou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Jiarui Lin

Conditions Rectal Cancer; Neoadjuvant therapy; rectal cancer; liposomal irinotecan; radiotherapy; immunotherapy