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

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Bevacizumab; Drug: Volrustomig; Drug: FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06792695

D798VC00001

2024-518469-84 (Registry Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Overall 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Volrustomig + FOLFIRI+ Bevacizumab group (Arm A)

Experimental group

Description:

Participants will receive FOLFIRI and bevacizumab together with volrustomig.

Treatment:

Drug: FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan)

Drug: Volrustomig

Drug: Bevacizumab

FOLFIRI+ BEVACIZUMAB group (Arm B)

Active Comparator group

Description:

Partcipants will receive FOLFIRI and bevacizumab.

Treatment:

Drug: FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan)

Drug: Bevacizumab