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

February 5, 2024 updated by: WeiWei Xiao, Sun Yat-sen University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

33

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Arm
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.
Radiation: Neoadjuvant Radiotherapy
IMRT DT: 50Gy/25Fx
Drug: AK104
During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.
Other Names:
  • Cadonilimab
Drug: Capecitabine
During neo-CRT: 825mg/m2 bid Monday-Friday per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response (CR) rate
Time Frame: an average of 6 months.
Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).
an average of 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease free survival
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.
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.
Local recurrence free survival
Time Frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
3 year local recurrence free survival rate
From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Adverse effects
Time Frame: From date of randomization until the date of death from any cause, assessed up to 5 years
Adverse effects according to CTCAE 5.0
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 Major pathologic response and tumor regression grade distribution
an average of 1 year.
Rate of surgical complications
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.
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.
Overall survival
Time Frame: From date of randomization until the date of death from any cause, assessed up to 60 months.
5 year overall survival rate
From date of randomization until the date of death from any cause, assessed up to 60 months.
Long-term anal function
Time Frame: 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)
1.5 year after diagnosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Collaborators

Akeso
Haplox Biotechnology Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 24, 2023

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

January 31, 2025

Study Registration Dates

First Submitted

July 26, 2023

First Submitted That Met QC Criteria

August 5, 2023

First Posted (Actual)

August 8, 2023

Study Record Updates

Last Update Posted (Actual)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2022-766-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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