Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
- Age 18-75
- ECOG 0-1
- Rectal adenocarcinoma
- cT3-4aNany or cT1-4aN+
- No distant metastasis
- Location ≤12 cm from the anal verge
- Positive PD-L1 expression (PD-L1 TPS≥1% or PD-L1 CPS ≥1)
- the MSI status is MSS and pMMR
- Sufficient bone marrow, kidney and liver function
- No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy, no immunotherapy
Exclusion Criteria:
- bowel obstruction
- Distant metastasis
- Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV )
- Uncontrollable severe hypertesion
- Active severe infection
- Cachexia, organ dysfunction
- Previous pelvic radiotherapy or chemotherapy
- Multiple primary cancers
- Epileptic seizures
- Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma
- Persons deprived of liberty or under guardianship
- Impossibility for compliance to follow-up
- Certain or suspicious allergy to research drug
- Pregnant or breast-feeding woman