Combining AK104 with Chemoradiotherapy for Advanced Rectal Cancer

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

Phase 2 Interventional Sun Yat-sen University · NCT05980689

This study is testing if adding a new treatment called AK104 to standard chemoradiotherapy can help people with advanced rectal cancer do better and have fewer side effects.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment33 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorSun Yat-sen University Academic / other
Drugs / interventionschemotherapy, immunotherapy, radiation
Locations1 site (Guangzhou, Guangdong)
Trial IDNCT05980689 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm study investigates the efficacy and safety of AK104, a bispecific antibody targeting PD1 and CTLA4, in conjunction with neoadjuvant chemoradiotherapy for patients with proficient Mismatch Repair (pMMR) and Microsatellite Stable (MSS) locally advanced rectal cancer. A total of 33 patients will receive long-course chemoradiotherapy along with 2 cycles of AK104, followed by an additional 3 cycles of AK104, before transitioning to standard clinical management. The study aims to analyze tumor response, adverse effects, and long-term prognosis associated with this treatment regimen.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with pMMR/MSS locally advanced rectal adenocarcinoma and no distant metastasis.

Not a fit: Patients with distant metastasis, severe comorbidities, or prior treatments that conflict with eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with locally advanced rectal cancer.

How similar studies have performed: While the combination of immunotherapy and chemoradiotherapy is a growing area of interest, this specific approach with AK104 in this patient population is novel and has not been extensively tested in prior studies.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Guangzhou, Guangdong

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Locally Advanced Rectal Cancer
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.