Trial: A Study of Novel Study Interventions an…

Trial Details

Sponsor: AstraZeneca (industry)

Phase: 2

Start date: March 12, 2025

Planned enrollment: 120

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Volrustomig (MEDI5752, PD-1/CTLA-4 DuetMab, MEDI-5752)

Overview

Volrustomig, also known as MEDI5752 or PD-1/CTLA-4 DuetMab, is an investigational bispecific monoclonal antibody targeting both PD-1 and CTLA-4 immune checkpoints. It is designed to fully inhibit PD-1 while preferentially inhibiting CTLA-4 on activated PD-1–positive T cells, aiming to enhance antitumor immune responses. (oncologypro.esmo.org)

Mechanism of Action

Volrustomig's bispecific nature allows it to simultaneously block PD-1 and CTLA-4 pathways. This dual inhibition is intended to restore and amplify T-cell activity against tumor cells, potentially leading to improved therapeutic outcomes compared to targeting either checkpoint alone. (aacrjournals.org)

Efficacy

In a Phase 1 study involving treatment-naïve patients with advanced clear cell renal cell carcinoma (ccRCC), volrustomig demonstrated promising efficacy:

750 mg dose cohort (V750):
Objective response rate (ORR): 48.4%
Complete response (CR) rate: 9.7%
Disease control rate (DCR): 90.3%
Median duration of response (DOR): 17.0 months
Median progression-free survival (PFS): 12.3 months
500 mg dose cohort (V500):
ORR: 45.5%
CR rate: 6.1%
DCR: 69.7%
Median DOR: 11.5 months
Median PFS: 9.7 months

These results suggest that volrustomig has the potential to improve outcomes in patients with advanced RCC. (onclive.com)

Safety

The safety profile of volrustomig is consistent with dual checkpoint inhibition:

750 mg dose cohort (V750):
Treatment-related adverse events (TRAEs) occurred in 96.9% of patients, with grade 3 or 4 TRAEs in 62.5%.
Common TRAEs included pruritus (50%), hyperthyroidism (34.4%), and diarrhea (25%).
46.9% of patients discontinued treatment due to TRAEs.
500 mg dose cohort (V500):
TRAEs occurred in 93.9% of patients, with grade 3 or 4 TRAEs in 42.4%.
Common TRAEs included pruritus (39.4%), hyperthyroidism (21.2%), and diarrhea (21.2%).
30.4% of patients discontinued treatment due to TRAEs.

One treatment-related death occurred in the V500 cohort due to bronchopulmonary aspergillosis with immune neutropenia. (onclive.com)

More Resources

Trial ID: NCT06792695

More trial details at ClinicalTrials.gov

Show News & AI Analysis

HealthScout AI Analysis

Goal: The trial aims to evaluate the safety and efficacy of novel combination therapies, particularly the addition of volrustomig to FOLFIRI and bevacizumab, in patients with colorectal cancer.

Patients: The study includes adults with histologically confirmed metastatic colorectal adenocarcinoma who are mismatch-repair proficient (pMMR) and microsatellite stable (MSS), have no liver metastases, measurable disease by RECIST 1.1, ECOG 0-1, and have not received prior systemic therapy for metastatic disease (excepting adjuvant/neoadjuvant therapy completed over 6 months prior). Key exclusions involve other malignancies, central nervous system metastases, significant autoimmune or cardiac diseases, and conditions increasing risk for bleeding or fistula.

Design: This is a multicenter, phase 2, open-label, randomized platform study with a master protocol and modular substudies. Patients are randomized to receive either the experimental combination or the active comparator.

Treatments: The experimental arm tests volrustomig, a novel monovalent bispecific antibody targeting PD-1 and CTLA-4 checkpoints, in combination with FOLFIRI (fluorouracil, leucovorin, irinotecan) and bevacizumab. Volrustomig has demonstrated promising anti-tumor activity in other solid tumor trials, including objective response rates over 45% in advanced renal cell carcinoma, and is designed to preferentially target CTLA-4 on activated PD-1+ T cells, potentially maximizing tumor-specific immune response while reducing peripheral toxicity. The active comparator arm uses FOLFIRI plus bevacizumab, a standard regimen in metastatic colorectal cancer.

Outcomes: Primary outcomes include progression-free survival (PFS) and the incidence of adverse events. Secondary outcomes are objective response rate (ORR), overall survival (OS), disease control rate (DCR), duration of response (DoR), time to second progression or death (PFS2), pharmacokinetics (peak and trough levels), and incidence of anti-drug antibodies.

Burden on patient: The patient burden is expected to be moderate to high due to requirements for tissue collection, frequent clinical and laboratory assessments, and regular imaging to monitor disease per RECIST 1.1. As an investigational agent is involved, additional pharmacokinetic blood draws and possibly immunogenicity assessments are likely, beyond those required for standard of care treatment. All therapy is given intravenously, necessitating regular clinic visits and monitoring for immune-related and general adverse events.

Eligibility

Show Criteria

Sites (75)

Sort by distance to:

Research Site

Woodville South, 5011, Australia

No email / No phone

Status: Recruiting

Research Site

Wollongong, 2500, Australia

No email / No phone

Status: Recruiting

Research Site

East Melbourne, 3002, Australia

No email / No phone

Status: Recruiting

Research Site

Victoria, British Columbia, V8R 6V5, Canada

No email / No phone

Status: Not yet recruiting

Research Site

Barrie, Ontario, L4M 6M2, Canada

No email / No phone

Status: Not yet recruiting

Research Site

Toronto, Ontario, M5G 1X6, Canada

No email / No phone

Status: Recruiting

Research Site

Montreal, Quebec, H3T 1E2, Canada

No email / No phone

Status: Not yet recruiting

Research Site

Beijing, 100142, China

No email / No phone

Status: Not yet recruiting

Research Site

Zhengzhou City, 450000, China

No email / No phone

Status: Not yet recruiting

Research Site

Wuhan, 430079, China

No email / No phone

Status: Not yet recruiting

Research Site

Shanghai, 201114, China

No email / No phone

Status: Not yet recruiting

Research Site

Shanghai, 200032, China

No email / No phone

Status: Not yet recruiting

Research Site

Shanghai, 200003, China

No email / No phone

Status: Not yet recruiting

Research Site

Harbin, 150081, China

No email / No phone

Status: Not yet recruiting

Research Site

Chengdu, 610041, China

No email / No phone

Status: Not yet recruiting

Research Site

Marseille Cedex 9, 13273, France

No email / No phone

Status: Not yet recruiting

Research Site

Montpellier, 34090, France

No email / No phone

Status: Not yet recruiting

Research Site

Montpellier, 34298, France

No email / No phone

Status: Not yet recruiting

Research Site

Poitiers, 86021, France

No email / No phone

Status: Not yet recruiting

Research Site

Villejuif Cedex, 94805, France

No email / No phone

Status: Not yet recruiting

Research Site

Saint-Priez En Jarez, 42270, France

No email / No phone

Status: Not yet recruiting

Research Site

Bordeaux, 33076, France

No email / No phone

Status: Not yet recruiting

Research Site

Essen, 45147, Germany

No email / No phone

Status: Not yet recruiting

Research Site

Berlin, 10117, Germany

No email / No phone

Status: Not yet recruiting

Research Site

Dresden, 01307, Germany

No email / No phone

Status: Not yet recruiting

Research Site

Hamburg, 22763, Germany

No email / No phone

Status: Not yet recruiting

Research Site

Marburg, 35043, Germany

No email / No phone

Status: Not yet recruiting

Research Site

Bologna, 40133, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Roma, 00168, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Pisa, 56100, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Pavia, 27100, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Napoli, 80131, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Milano, 20162, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Milano, 20133, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Firenze, 50134, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Castelfranco Veneto, 31033, Italy

No email / No phone

Status: Not yet recruiting

Research Site

Seoul, 5505, Korea, Republic of

No email / No phone

Status: Recruiting

Research Site

Seoul, 03080, Korea, Republic of

No email / No phone

Status: Recruiting

Research Site

Seoul, 06351, Korea, Republic of

No email / No phone

Status: Recruiting

Research Site

Seoul, 06591, Korea, Republic of

No email / No phone

Status: Recruiting

Research Site

Yongin-si, 16995, Korea, Republic of

No email / No phone

Status: Recruiting

Research Site

Maastricht, 6202 AZ, Netherlands

No email / No phone

Status: Not yet recruiting

Research Site

Amsterdam, 1066 CX, Netherlands

No email / No phone

Status: Not yet recruiting

Research Site

Zwolle, 8025 AB, Netherlands

No email / No phone

Status: Not yet recruiting

Research Site

Madrid, 28041, Spain

No email / No phone

Status: Not yet recruiting

Research Site

Malaga, 29010, Spain

No email / No phone

Status: Not yet recruiting

Research Site

Pamplona, 31005, Spain

No email / No phone

Status: Not yet recruiting

Research Site

Santander, 39008, Spain

No email / No phone

Status: Not yet recruiting

Research Site

València, 46010, Spain

No email / No phone

Status: Not yet recruiting

Research Site

Barcelona, 8003, Spain

No email / No phone

Status: Recruiting

Research Site

Barcelona, 08035, Spain

No email / No phone

Status: Not yet recruiting

Research Site

Madrid, 28007, Spain

No email / No phone

Status: Not yet recruiting

Research Site

Madrid, 28034, Spain

No email / No phone

Status: Not yet recruiting

Research Site

Taoyuan, 333, Taiwan

No email / No phone

Status: Recruiting

Research Site

Kaohsiung, 80756, Taiwan

No email / No phone

Status: Recruiting

Research Site

Taipei, 10002, Taiwan

No email / No phone

Status: Not yet recruiting

Research Site

Yung Kang City, 71044, Taiwan

No email / No phone

Status: Recruiting

Research Site

Cambridge, CB2 0XY, United Kingdom

No email / No phone

Status: Not yet recruiting

Research Site

London, NW1 2PG, United Kingdom

No email / No phone

Status: Recruiting

Research Site

London, W12 0HS, United Kingdom

No email / No phone

Status: Recruiting

Research Site

Manchester, M20 4GJ, United Kingdom

No email / No phone

Status: Not yet recruiting

Research Site

Wirral, CH63 4JY, United Kingdom

No email / No phone

Status: Not yet recruiting

Research Site

Scottsdale, Arizona, 85259, United States

No email / No phone

Status: Not yet recruiting

Research Site

Los Angeles, California, 90089, United States

No email / No phone

Status: Not yet recruiting

Research Site

Washington, District of Columbia, 20007, United States

No email / No phone

Status: Not yet recruiting

Research Site

Chicago, Illinois, 60637, United States

No email / No phone

Status: Not yet recruiting

Research Site

Baltimore, Maryland, 21224, United States

No email / No phone

Status: Recruiting

Research Site

Boston, Massachusetts, 02114, United States

No email / No phone

Status: Not yet recruiting

Research Site

Rochester, Minnesota, 55905, United States

No email / No phone

Status: Not yet recruiting

Research Site

Rochester, New York, 14618, United States

No email / No phone

Status: Not yet recruiting

Research Site

Cleveland, Ohio, 44106, United States

No email / No phone

Status: Withdrawn

Research Site

Portland, Oregon, 97239, United States

No email / No phone

Status: Not yet recruiting

Research Site

Philadelphia, Pennsylvania, 19104, United States

No email / No phone

Status: Withdrawn

Research Site

Nashville, Tennessee, 37232, United States

No email / No phone

Status: Not yet recruiting

Research Site

Houston, Texas, 77030, United States

No email / No phone

Status: Not yet recruiting

A Phase II, Open-label, Multicenter, Master Protocol to Evaluate the Safety and Efficacy of Novel Study Interventions and Combinations in Participants With Colorectal Cancer (CANTOR)

Trial Details

Show Summary from Sponsor

More details:

Investigational Drug AI Analysis

Show for: Volrustomig (MEDI5752, PD-1/CTLA-4 DuetMab, MEDI-5752)

Overview

Mechanism of Action

Efficacy

Safety

Further Reading

More Resources

Show News & AI Analysis

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (75)

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site