A Study of Novel Study Interventions and Combinations in Participants With Colorectal Cancer

Phase 2

Recruiting

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Volrustomig; Drug: Bevacizumab; Drug: FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan)

• Registration Number: NCT06792695
• Lead Sponsor: AstraZeneca

Brief Summary

The main purpose of this study is to evaluate the safety and efficacy of novel study interventions and combinations in participants with Colorectal Cancer (CRC).

Detailed Description

This is a Phase II, platform, open-label, multi-drug, multicenter, global study.

This is a modular study, that includes a master protocol and substudies.

Partcipants will be randomised to one of the following intervention groups:

* Volrustomig + FOLFIRI + bevacizumab group (Arm A)

* FOLFIRI + bevacizumab group (Arm B)

The substudy will evaluate the effects of volrustomig in combination with FOLFIRI (irinotecan, 5-FU, and leucovorin) and bevacizumab versus FOLFIRI and bevacizumab only in participants with Mismatch-repair-proficient (pMMR)/Microsatellite stable (MSS) metastatic CRC (mCRC) in the absence of liver metastases and who have not received previous systemic treatment for advanced or metastatic disease.

Study Timeline

• Study First Submitted: 2025-01-20
• Study First Submitted QC: 2025-01-20
• Study First Posted: 2025-01-27
• Study Start: 2025-03-12
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-15
• Primary Completion: 2027-03-24
• Study Completion: 2028-01-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Histopathologically confirmed colorectal adenocarcinoma.
• Provision of FFPE tumor sample collected as per SoC.
• Presence of measurable disease by RECIST 1.1 criteria.
• ECOG performance status of 0 or 1.
• Life expectancy ≥ 12 weeks at the time of screening.

Substudy Inclusion Criteria:

• No radiological evidence of liver metastasis.
• No prior systemic therapy for mCRC, except for neoadjuvant/adjuvant chemotherapy where, > 6 months have elapsed between completion of therapy and documented date of diagnosis of recurrent or metastatic disease.
• Known pMMR/MSS status (only pMMR/MSS mCRC allowed).
• Adequate organ and bone marrow function
• Body weight > 35 kg at screening and at randomization.
• Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Overall

Exclusion Criteria

• Central nervous system metastases or spinal cord compression
• Known history of severe allergy to any monoclonal antibody or study intervention.
• Any unresolved toxicity CTCAE Grade ≥ 2 from a previous anticancer therapy.
• History of another primary malignancy.

Substudy Exclusion Criteria:

• Potentially resectable disease with multidisciplinary plan for radical surgery.
• Active or prior documented autoimmune or inflammatory disorders or cardiac conditions.
• Participants with a prior history of hypertensive crisis or hypertensive encephalopathy or bleeding risks.
• Deep venous thrombosis, pulmonary embolism, arterial thrombosis, transient ischemic attack or cerebrovascular accident.
• History of abdominal or tracheoesophageal fistula, GI perforation and/or fistulae, or intraabdominal abscess within 6 months prior to randomization.
• Prior exposure to immune mediated therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Volrustomig + FOLFIRI+ Bevacizumab group (Arm A)	Volrustomig	Participants will receive FOLFIRI and bevacizumab together with volrustomig.
FOLFIRI+ BEVACIZUMAB group (Arm B)	Bevacizumab	Partcipants will receive FOLFIRI and bevacizumab.
Volrustomig + FOLFIRI+ Bevacizumab group (Arm A)	FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan)	Participants will receive FOLFIRI and bevacizumab together with volrustomig.
Volrustomig + FOLFIRI+ Bevacizumab group (Arm A)	Bevacizumab	Participants will receive FOLFIRI and bevacizumab together with volrustomig.
FOLFIRI+ BEVACIZUMAB group (Arm B)	FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan)	Partcipants will receive FOLFIRI and bevacizumab.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Approximately 3 years	PFS is defined as the time from randomization until progression per Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) or death due to any cause.
Number of Participants with Adverse Events (AEs)	Approximately 3 years	Number of participants who received at least one dose of study treatment will be assessed.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Approximately 3 years	OS is defined as the time from randomization until the date of death due to any cause.
Objective Response Rate (ORR)	Approximately 3 years	ORR is defined as the proportion of participants who have a confirmed complete response or confirmed partial response as per RECIST 1.1.
Disease Control Rate (DCR)	Approximately 3 years	DCR is defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST 1.1 after randomization.
Duration of Response (DOR)	Approximately 3 years	DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 or death due to any cause.
Time to second progression or death (PFS2)	Approximately 3 years	PFS2 is defined as the time from randomization to the earliest of the progression event, after first subsequent therapy, or death.
Maximum Observed Concentration (Cmax)	Approximately 3 years	Concentration of novel study intervention in serum and PK parameters as data allow (such as peak and trough concentrations) will be assessed.
Observed lowest concentration before the next dose is administered (Ctrough)	Approximately 3 years	Concentration of novel study intervention in serum and PK parameters as data allow (such as peak and trough concentrations) will be assessed.
Number of patients with positive Antidrug Antibodies (ADAs)	Approximately 3 years	The immunogenicity (ADAs) of novel study intervention in participants with CRC in the absence of liver metastases is investigated.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Wirral, United Kingdom