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

Locally Advanced Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05980689
• Other study ID #: B2022-766-01
• Status: Recruiting
• Phase: Phase 2
• Start date: October 24, 2023
• Est. completion date: January 31, 2025

Study information

• Verified date: February 2024
• Source: Sun Yat-sen University
• Contact: WeiWei Xiao
• Phone: 8613710390520
• Email: xiaoww[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. completion date: January 31, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• AK104
During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.
• Capecitabine
During neo-CRT: 825mg/m2 bid Monday-Friday per week

Radiation:
• Neoadjuvant Radiotherapy
IMRT DT: 50Gy/25Fx

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Sun Yat-sen University	Akeso, Haplox Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response (CR) rate	Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).	an average of 6 months.
Secondary	Adverse effects	Adverse effects according to CTCAE 5.0	From date of randomization until the date of death from any cause, assessed up to 5 years
Secondary	Rate of Major pathologic response and tumor regression grade distribution	Rate of Major pathologic response and tumor regression grade distribution	an average of 1 year.
Secondary	Rate of surgical complications	Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.	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.
Secondary	Disease free survival	3 year disease free survival rate	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.
Secondary	Local recurrence free survival	3 year local recurrence free survival rate	From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Secondary	Overall survival	5 year overall survival rate	From date of randomization until the date of death from any cause, assessed up to 60 months.
Secondary	Long-term anal function	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)	1.5 year after diagnosis