Cadonilimab in Locally Advanced MSI-H/dMMR Colorectal Cancer

A Phase II Trial of Cadonilimab in Locally Advanced Stage II/III MSI-H/dMMR Colorectal Cancer

This is a two-arm phase II clinical study to evaluate the efficacy and safety of Cadonilimab (a PD-1/CTLA-4 bispecific antibody) in MSI-H/dMMR locally advanced colorectal cancer as the regimen of neoadjuvant treatment. Eligible patients will receive Cadonilimab monotherapy for eight cycles before surgery and part of patients may exempt from surgery.

Study Overview

• Status: Recruiting
• Conditions: dMMR Colorectal Cancer
• Intervention / Treatment: Drug: Cadonilimab

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aiping Zhou, M.D.; Phone Number: 86-10-87788800; Email: zhouap1825@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
      • Contact: Aiping Zhou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Arm 1: Histologically or pathologically confirmed colon adenocarcinoma with a stage of T3-4 or N+ according to the CT or endoscope; Arm 2: Histologically or pathologically confirmed rectal adenocarcinoma located within 12cm from the anus with a stage of T2-4 or N+ according to the CT or endoscope
• Sign the informed consent form
• 18 years and older
• Mismatch repair deficient determined by immunohistochemistry or microsatellite instable by PCR
• No prior treatment
• Performance status: ECOG 0-1
• Good organ function:

Blood routine: hemoglobin ≥90g/L, neutrophil ≥1.5×10^9/L, platelet ≥80×10^9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥50ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL; Ejection fraction at least 50% (or lower limit of normal) by echocardiogram

Exclusion Criteria:

• Other pathological category, such as squamous cancer
• Distant metastasis or peritoneum implantation
• Have received chemotherapy or radiotherapy in the past
• Known to have allergic reactions to any ingredients or excipients of experimental drugs
• Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment
• Have received colorectal cancer surgery
• Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug
• Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months
• Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C
• Pregnant or nursing
• May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results
• There are other serious diseases that the researchers believe patients cannot be included in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dMMR/MSI-H colon cancer	Drug: Cadonilimab; Cadonilimab 10mg/kg iv on day 1 for every 21 days with a total of 8 cycles
Experimental: dMMR/MSI-H rectal cancer	Drug: Cadonilimab; Cadonilimab 10mg/kg iv on day 1 for every 21 days with a total of 8 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response rate	For colon cancer arm, complete response rate include the rate of pathological complete response and clinical complete response; for rectal cancer arm, complete response rate means the rate of clinical complete response	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	From date of initiation of treatment to date of death due to any cause, assessed up to 3 years
DFS	Disease free survival	From date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 3 years
pCR rate	The rate of pathologic complete response for patients receiving surgery	2 year

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Anticipated): September 30, 2024
• Study Completion (Anticipated): March 30, 2026

Study Registration Dates

• First Submitted: April 1, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: NCC3626

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No