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

Phase 2

Recruiting

• Conditions: Locally Advanced Rectal Cancer
• Interventions: Drug: AK104; Drug: Capecitabine; Radiation: Neoadjuvant Radiotherapy

• Registration Number: NCT05980689
• Lead Sponsor: Sun Yat-sen University

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.

Study Timeline

• Study First Submitted: 2023-07-26
• Study First Submitted QC: 2023-08-05
• Study First Posted: 2023-08-08
• Study Start: 2023-10-24
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-05
• Last Update Posted: 2024-02-07
• Primary Completion: 2024-06-30
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 33

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Neoadjuvant Radiotherapy	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.
Treatment Arm	AK104	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.
Treatment Arm	Capecitabine	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.

Primary Outcome Measures

Name	Time	Method
Complete response (CR) rate	an average of 6 months.	Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).

Secondary Outcome Measures

Name	Time	Method
Adverse effects	From date of randomization until the date of death from any cause, assessed up to 5 years	Adverse effects according to CTCAE 5.0
Overall survival	From date of randomization until the date of death from any cause, assessed up to 60 months.	5 year overall survival rate
Local recurrence free survival	From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.	3 year local recurrence free survival rate
Rate of surgical complications	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.	Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Rate of Major pathologic response and tumor regression grade distribution	an average of 1 year.	Rate of Major pathologic response and tumor regression grade distribution
Disease free survival	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.	3 year disease free survival rate
Long-term anal function	1.5 year after diagnosis	Long-term anal function was evaluated using the Wexner Continence Grading Scale ,the score being calculated after the patients' completion of a daily defecatory questionnaire. Range is from 0 (normal continence) to 20 (maximum incontinence with maximum disturbance of lifestyle)

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China