XELOX Combined With Cadonilimab Versus XELOX as Neoadjuvant Treatment for Locally Advanced, pMMR Rectal Cancer

Study Overview
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Brief Summary
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This is a two-arm, open label, randomized phase II clinical study. The aim is to evaluate the safety and efficacy of Cadonilimab (a PD-1/CTLA-4 bispecific antibody) combined with XELOX regimen in pMMR locally advanced rectal cancer during the perioperative period. Eligible patients will receive either Cadonilimab plus XELOX or XELOX alone for 4 cycles before and 4 cycles after surgery. The primary endpoint is the pathological complete response rate.

Official Title
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XELOX Combined With Cadonilimab Versus XELOX as Neoadjuvant Treatment for MRF-negative Locally Advanced, pMMR Rectal Cancer: a Randomised, Phase 2 Trial

Conditions
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MSS, Rectal Cancer

Intervention / Treatment
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* Drug: Cadonilimab
* Drug: Oxaliplatin
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or pathologically confirmed rectal adenocarcinoma located within 5 to 15cm from the anus with a stage of T3-4a or N+ according to the CT or endoscope Mesorectal fascia uninvolved Sign the informed consent form 18 years and older Mismatch repair proficient determined by immunohistochemistry No prior treatment Performance status: ECOG 0-1 Good organ function: Blood routine: hemoglobin ≥90g/L, neutrophil ≥1.5×10^9/L, platelet ≥100×10^9/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 Unable to swallow or under other circumstance which would drug absorption 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cadonilimab + XELOX<br>Oxaliplatin 130 mg/m2 iv and Cadonilimab 10mg/kg iv on day 1； Capecitabine 1000mg/m2 po bid on day 1 to 14； every 21 day as a cycle, 4 cycles before surgery and 4 cycles after surgery | Drug: Cadonilimab<br>* 10mg/kg iv on day 1, every 21 day<br>Drug: Oxaliplatin<br>* 130mg/m2 iv on day 1, every 21 day<br>Drug: Capecitabine<br>* 1000mg/m2 po bid on day 1 to 14, every 21 day<br>|
| Sham Comparator: XELOX<br>Oxaliplatin 130 mg/m2 iv on day 1； Capecitabine 1000mg/m2 po bid on day 1 to 14； every 21 day as a cycle, 4 cycles before surgery and 4 cycles after surgery | Drug: Oxaliplatin<br>* 130mg/m2 iv on day 1, every 21 day<br>Drug: Capecitabine<br>* 1000mg/m2 po bid on day 1 to 14, every 21 day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR | the rate of pathological complete response | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MPR | the rate of major pathological response according to Becker-TRG | 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 | 
| OS | overall survival | From date of initiation of treatment to date of death, assessed up to 3 years |