Clinical trial NCT05980689: Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer
Official title: A Phase II Trial of AK104 Combined With Neoadjuvant Chemoradiotherapy in Proficient Mismatch Repair/Microsatellite Stable Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Akeso
name: Haplox Biotechnology Co., Ltd.
First posted: 2023-08-08
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 criteria: 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

Primary outcomes:
measure: Complete response (CR) rate
timeFrame: an average of 6 months.
Secondary outcomes:
measure: Adverse effects
timeFrame: From date of randomization until the date of death from any cause, assessed up to 5 years
measure: Rate of Major pathologic response and tumor regression grade distribution
timeFrame: an average of 1 year.
measure: Rate of surgical complications
timeFrame: The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 1 year from the surgery.
measure: Disease free survival
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
measure: Local recurrence free survival
timeFrame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 60 months.
measure: Long-term anal function
timeFrame: 1.5 year after diagnosis
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: