Cadonilimab Plus FOLFOXIRI and Bevacizumab as First Line Therapy for Metastatic MSS Colorectal Cancer

Study Overview
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Brief Summary
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Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in tumors. This was a phase II study of cadonilimab in combination with bevacizumab and FOLFOXIRI as first line therapy for metastatic microsatellite stable (MSS) colorectal cancer. The goal of this clinical trial is to evaluated the efficacy and safety.

Detailed Description
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Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in tumors. This was a phase II study of cadonilimab in combination with bevacizumab and FOLFOXIRI as first line therapy in patients with metastatic microsatellite stable (MSS) colorectal cancer. The goal of this clinical trial is to evaluated the efficacy and safety. Cadonilimab (6mg/kg, iv, Q2W, Day1)+irinotecan* 165 mg/m² iv continue for 1.5 hours, D1; oxaliplatin 85 mg/m² iv continue for 2 hours, D1; leucovorin 400 or levoleucovorin 200 mg/m² iv continue for 2 hours, D1; 5-FU 2400 mg/m² cont. inf. 48h; repeat every 2 weeks (Q2W) + bevacizumab （5mg/kg，d 1）

Official Title
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A Phase II, Prospective, Multicenter Study of Cadonilimab in Combination With FOLFOXIRI and Bevacizumab as First Line Therapy for Metastatic MSS Colorectal Cancer.

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: cadonilimab
* Drug: irinotecan
* Drug: Oxaliplatin
* Drug: leucovorin or levoleucovorin
* Drug: 5-FU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with metastatic pMMR or MSS colorectal adenocarcinoma. Note: MMR or MSI status will be performed locally by an immunohistochemistry (IHC) or PCR based test for eligibility. Patients who are naïve to systemic treatment in metastatic setting. Patients with previous neoadjuvant or adjuvant chemotherapy (that may have included oxaliplatin or investigational VEGF inhibitors) are eligible if the treatment was completed > 12 months before inclusion. Patients with the presence of at least one lesion with measurable disease as per RECIST 1.1 guidelines. Lesions in previously irradiated areas should not be considered measurable unless they have clearly progressed since the radiotherapy. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Exclusion Criteria: Patients with MSI-H colorectal adenocarcinoma as defined per local assessment using standard of care testing Patients with metastatic disease amenable to be resected with potentially curative surgery Patients who have received any systemic treatment for metastatic disease. Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti-CTLA-4 antibodies, other checkpoint inhibitors Patients who had received radiation within 14 days prior to the first dose of study drug

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cadonilimab+ FOLFOXIRI+bevacizumab<br>Cadonilimab (6mg/kg, iv, Q2W, Day1)+irinotecan* 165 mg/m² iv continue for 1.5 hours, D1; oxaliplatin 85 mg/m² iv continue for 2 hours, D1; leucovorin 400 or levoleucovorin 200 mg/m² iv continue for 2 hours, D1; 5-FU 2400 mg/m² cont. inf. 48h; repeat every 2 weeks (Q2W) + bevacizumab （5mg/kg，d 1） | Drug: cadonilimab<br>* Cadonilimab (6mg/kg, iv, Q2W, Day1)<br>Drug: irinotecan<br>* irinotecan* 165 mg/m² iv continue for 1.5 hours, D1<br>Drug: Oxaliplatin<br>* oxaliplatin 85 mg/m² iv continue for 2 hours,<br>Drug: leucovorin or levoleucovorin<br>* leucovorin 400 or levoleucovorin 200 mg/m² iv continue for 2 hours<br>Drug: 5-FU<br>* 5-FU 2400 mg/m² cont. inf. 46h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | RECIST 1.1 | Up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | RECIST 1.1 | Up to two years |