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

Phase 2

Recruiting

• Conditions: Colorectal Cancer
• Interventions: Drug: cadonilimab; Drug: irinotecan; Drug: Oxaliplatin; Drug: leucovorin or levoleucovorin; Drug: 5-FU

• Registration Number: NCT05839470
• Lead Sponsor: Fujian Cancer Hospital

Brief Summary

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

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）

Study Timeline

• Study First Submitted: 2023-04-19
• Study First Submitted QC: 2023-04-20
• Study First Posted: 2023-05-03
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-11
• Last Update Posted: 2023-11-15
• Study Start: 2023-11-19
• Primary Completion: 2024-03-01
• Study Completion: 2025-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cadonilimab+ FOLFOXIRI+bevacizumab	leucovorin or levoleucovorin	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）
Cadonilimab+ FOLFOXIRI+bevacizumab	5-FU	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）
Cadonilimab+ FOLFOXIRI+bevacizumab	cadonilimab	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）
Cadonilimab+ FOLFOXIRI+bevacizumab	irinotecan	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）
Cadonilimab+ FOLFOXIRI+bevacizumab	Oxaliplatin	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）

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to two years	RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	Up to two years	RECIST 1.1

Trial Locations

Locations (1)

Fujian Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China