Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer

A Phase II Trial of AK104 Combined With Neoadjuvant Chemoradiotherapy in Proficient Mismatch Repair/Microsatellite Stable Locally Advanced Rectal Cancer

This is an open-label, single-arm study to investigate the efficacy and safety of AK104 (an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) and neoadjuvant chemoradiotherapy in patients with pMMR/MSS locally advanced rectal cancer.

The study evaluates the addition of AK104(an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) in neoadjuvant chemoradiotherapy in proficient Mismatch Repair (pMMR) /Microsatellite Stable (MSS) locally advanced rectal cancer (LARC). A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage. The tumor response to treatment, adverse effects and long-term prognosis will be analyzed.

Inclusion Criteria:

1. Age 18-75
2. ECOG 0-1
3. Rectal adenocarcinoma
4. cT3-4aNany or cT1-4aN+
5. No distant metastasis
6. Location ≤12 cm from the anal verge
7. Positive PD-L1 expression (PD-L1 TPS≥1% or PD-L1 CPS ≥1)
8. the MSI status is MSS and pMMR
9. Sufficient bone marrow, kidney and liver function
10. No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy, no immunotherapy

Exclusion Criteria:

1. bowel obstruction
2. Distant metastasis
3. Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV )
4. Uncontrollable severe hypertesion
5. Active severe infection
6. Cachexia, organ dysfunction
7. Previous pelvic radiotherapy or chemotherapy
8. Multiple primary cancers
9. Epileptic seizures
10. Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma
11. Persons deprived of liberty or under guardianship
12. Impossibility for compliance to follow-up
13. Certain or suspicious allergy to research drug
14. Pregnant or breast-feeding woman