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

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ClinicalTrials.gov Identifier: NCT05980689
Recruitment Status : Recruiting
First Posted : August 8, 2023
Last Update Posted : February 7, 2024
Sponsor:
Collaborators:
Akeso
Haplox Biotechnology Co., Ltd.
Information provided by (Responsible Party):
WeiWei Xiao, Sun Yat-sen University

Study Description
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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.

Condition or disease Intervention/treatment Phase
Locally Advanced Rectal Cancer Drug: AK104 Drug: Capecitabine Radiation: Neoadjuvant Radiotherapy Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of AK104 Combined With Neoadjuvant Chemoradiotherapy in Proficient Mismatch Repair/Microsatellite Stable Locally Advanced Rectal Cancer
Actual Study Start Date : October 24, 2023
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : January 31, 2025
Arms and Interventions
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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.
 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 Name: Cadonilimab

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

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


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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)


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05980689


Contacts
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Contact: WeiWei Xiao 8613710390520 ext 8613710390520 xiaoww@sysucc.org.cn

Locations
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China, Guangdong
Sun Yat-sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: WeiWei xiao    8613710390520 ext 8613710390520    xiaoww@sysucc.org.cn   
Sponsors and Collaborators
Sun Yat-sen University
Akeso
Haplox Biotechnology Co., Ltd.
More Information
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Responsible Party: WeiWei Xiao, Chief physician, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT05980689    
Other Study ID Numbers: B2022-766-01
First Posted: August 8, 2023    Key Record Dates
Last Update Posted: February 7, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
 Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents