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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: cadonilimab; Drug: irinotecan; Drug: Oxaliplatin; Drug: leucovorin or levoleucovorin; Drug: 5-FU

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rongbo Lin; Phone Number: 0591-83660063; Email: rongbo_lin@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: Rongbo Lin; Phone Number: 0591-83660063; Email: rongbo_lin@163.com

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 19, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 11, 2023
• Last Verified: November 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Oxaliplatin; Leucovorin; Irinotecan; Levoleucovorin
• Other Study ID Numbers: SYLT-026

Drug and device information, study documents

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