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

Purpose

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).

Condition

  • Metastatic Colorectal Cancer

Eligibility

Eligible Ages
Between 18 Years and 130 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Volrustomig + FOLFIRI+ Bevacizumab group (Arm A) 		Participants will receive FOLFIRI and bevacizumab together with volrustomig.
  • Drug: Volrustomig
    Volrustomig will be administered as intravenous (IV) infusion.
    Other names:
    • MEDI5752
  • Drug: FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan)
    FOLFIRI will be administered as IV infusion.
  • Drug: Bevacizumab
    Bevacizumab will be administered as IV infusion.
Active Comparator
FOLFIRI+ BEVACIZUMAB group (Arm B) 		Partcipants will receive FOLFIRI and bevacizumab.
  • Drug: FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan)
    FOLFIRI will be administered as IV infusion.
  • Drug: Bevacizumab
    Bevacizumab will be administered as IV infusion.

Recruiting Locations

Research Site
Scottsdale, Arizona 85259

Research Site
Los Angeles, California 90089

Research Site
Baltimore, Maryland 21224

Research Site
Rochester, Minnesota 55905

Research Site
Rochester, New York 14618

Research Site
Houston, Texas 77030

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

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.