Total neoadjuvant therapy with concurrent tislelizumab for low rectal cancer

A Single-arm, Multicenter, Phase II Clinical Study of Total Neoadjuvant Therapy Plus Concurrent Tislelizumab Immunotherapy in Resectable Low Rectal Cancer

This trial tests whether adding the immunotherapy drug tislelizumab to total neoadjuvant chemotherapy helps adults with low rectal cancer reach a complete response so some can avoid major surgery.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: tislelizumab, immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07561060 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm multi-center study gives all participants 4–6 cycles of total neoadjuvant therapy combined with the PD-1 antibody tislelizumab, followed by a clinical response assessment. Patients who achieve a complete response (clinical CR or pathologic CR after local resection for near-CR) continue tislelizumab plus CAPOX for four more cycles and then receive tislelizumab alone for nine cycles before entering a Watch-and-Wait program. Patients who do not reach CR proceed to standard total mesorectal excision (TME). Key eligibility includes adults 18–75 with histologically confirmed low rectal adenocarcinoma within 3 cm of the dentate line, resectable cT1–3 N0–1 M0 disease, pMMR or MSS/MSI-L status, ECOG 0–1, and no prior anti-tumor treatment.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 with resectable low rectal adenocarcinoma (within 3 cm of the dentate line), cT1–3 N0–1 M0, pMMR or MSS/MSI-L, ECOG 0–1, and no prior rectal cancer treatment.

Not a fit: Patients with more advanced or metastatic disease (e.g., T4, N2, or M1), dMMR/MSI-H tumors, tumors located farther from the anal verge, or those unfit for chemotherapy or immunotherapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the approach could increase complete response rates and allow more patients to preserve their rectum and avoid major surgery.

How similar studies have performed: Other trials combining PD-1 inhibitors with neoadjuvant chemotherapy or chemoradiation have shown promising increases in complete response—particularly in MSI-H tumors—but benefit for pMMR/MSS rectal cancer remains exploratory.

Eligibility criteria

Inclusion Criteria:

1. Able to provide written informed consent, understand and comply with the requirements and evaluation schedule
2. ≥18, ≤75 years old
3. Histologically confirmed rectal adenocarcinoma
4. immunohistochemistry confirmed pMMR (positive for MLH1, MSH2, MSH6 and PMS2), or PCR /NGS confirmed MSI-L or MSS
5. The tumor is within 3 cm of the dentate line. through colonoscopy, digital anal examination or MRI
6. clinical stage cT1-3 N 0-1M0 (the 8th UICC/AJCC; T and N is evaluated by MRI)
7. Resectable primary tumor assessed by the Investigator
8. Have not received any anti-tumor treatment for rectal cancer
9. ECOG PS ≤ 1
10. Adequate organ function
11. Female subjects with the ability to become pregnant must have a serum pregnancy test with a negative result within 72 hours before the first dose, and be willing to use highly effective contraceptive methods during the trial and 120 days after the last dose. Male subjects whose partners are women of childbearing potential should be surgically sterilized or agree to use a highly effective method of contraception during the trial and for 120 days after the last dose.

Exclusion Criteria:

1. Histologically confirmed poorly differentiated/undifferentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma
2. Have received any treatments for rectal cancer, or evidence of distant metastasis
3. Presence of following high risk factors assessed by MRI: MRF +, EMVI+, cN2, Positive lateral lymph nodes, T3d
4. Presence or in high risk of obstruction, perforation or bleeding;
5. Not suitable for long-course radiotherapy
6. Cannot tolerate surgery
7. ≥2 colorectal cancer lesions at the same time
8. Contraindications for MRI examination
9. Other malignant tumors in the past or at the same time
10. Have an active autoimmune disease requiring systemic therapy within the past 2 years
11. HIV infection
12. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA \> 500 IU/mL) or active HCV carriers with detectable HCV RNA;
13. Hypersensitivity to any ingredient of tislelizumab, capecitabine, and oxaliplatin or to any component of the container
14. Other conditions judged by the researcher that do not meet the enrollment requirements

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Zhongshan Hospital, Shanghai — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Jianmin Xu, MD

Conditions Rectal Cancer