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

Sun Yat-sen University33 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Locally Advanced Rectal Cancer

Interventions

AK104DRUG

During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.

CapecitabineDRUG

During neo-CRT: 825mg/m2 bid Monday-Friday per week

Neoadjuvant RadiotherapyRADIATION

IMRT DT: 50Gy/25Fx

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

Outcomes

Primary Outcomes

Complete response (CR) rate

Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).

Time frame: an average of 6 months.

Secondary Outcomes

Adverse effects

Adverse effects according to CTCAE 5.0

Time frame: From date of randomization until the date of death from any cause, assessed up to 5 years

Rate of Major pathologic response and tumor regression grade distribution

Time frame: an average of 1 year.

Rate of surgical complications

Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.

Time frame: 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.

Disease free survival

3 year disease free survival rate

Time frame: 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.

Local recurrence free survival

3 year local recurrence free survival rate

Time frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.

Overall survival

5 year overall survival rate

Time frame: From date of randomization until the date of death from any cause, assessed up to 60 months.

Central Contacts

WeiWei Xiao

CONTACT

8613710390520 xiaoww@sysucc.org.cn

Data from ClinicalTrials.gov

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