Trial: A Study of Novel Study Interventions an…

Trial Details

Sponsor: AstraZeneca (industry)

Phase: 2

Start date: March 12, 2025

Planned enrollment: 120

Trial ID: NCT06792695

More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

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

Overview

Volrustomig (MEDI5752) is an investigational, humanized, monovalent bispecific IgG1 antibody that targets PD‑1 and CTLA‑4. It is being studied across multiple tumor types, including renal cell carcinoma (RCC), non–small cell lung cancer (NSCLC), pleural mesothelioma, hepatobiliary cancers, and head and neck cancer, in phases 1–3. Early clinical data show antitumor activity, with ongoing efforts to optimize dose to balance efficacy and immune‑related toxicities. (aacrjournals.org)

Mechanism of action

Volrustomig binds PD‑1 and CTLA‑4 with a “DuetMab” monovalent bispecific format engineered to fully block PD‑1 while preferentially inhibiting CTLA‑4 on activated PD‑1–positive T cells within tumors. This design enhances CTLA‑4 engagement in the tumor microenvironment and reduces activity on PD‑1–negative peripheral T cells. Tethering CTLA‑4 to PD‑1 also drives rapid internalization and degradation of PD‑1, providing a distinct mechanism from conventional separate PD‑1 and CTLA‑4 monoclonal antibodies. The Fc region is engineered to reduce effector function. (aacrjournals.org)

Efficacy

Advanced clear‑cell RCC (first‑line, monotherapy): In a phase 1 expansion (NCT03530397), volrustomig 1,500 mg Q3W produced an ORR of 38.5% in all expansion patients (n=26) and 58.3% in the first‑line ccRCC subset (n=12); median duration of response, PFS, and OS were not reached at 14.6 months’ follow‑up in the first‑line subset. Subsequent first‑line cohorts tested lower fixed doses. At ESMO 2023, ORR was 46.9% with 750 mg (n=32) and 45.5% with 500 mg (n=33); complete responses 9.4% and 6.1%, respectively; median PFS 11.1 and 9.9 months. (ascopubs.org)
Metastatic non‑squamous NSCLC (first‑line, with chemotherapy): In ESMO 2022 LBA56 (phase 1b/2, NCT03530397), volrustomig 1,500 mg + carboplatin/pemetrexed improved median PFS (15.1 vs 8.9 mo), DOR (20.5 vs 9.9 mo), and OS (not reached vs 16.5 mo) versus pembrolizumab + chemotherapy in a small randomized signal‑finding cohort (n=41). A separate single‑arm cohort using 750 mg + chemotherapy showed emerging ORR 44% overall and 48% in PD‑L1 <1% with improved tolerability at ~3.9 months’ follow‑up. A phase 3 trial (eVOLVE‑Lung02) is comparing volrustomig + chemotherapy vs pembrolizumab + chemotherapy in PD‑L1 <50% mNSCLC. (oncologypro.esmo.org)
Ongoing phase 3 programs: Volrustomig + carboplatin/pemetrexed is being compared against platinum/pemetrexed or nivolumab/ipilimumab in unresectable pleural mesothelioma; additional phase 3 evaluation is underway as consolidation after chemoradiotherapy in locally advanced head and neck squamous cell carcinoma. Results are pending. (mayo.edu)
Other tumor settings under study: Master protocols include combinations in hepatocellular and biliary tract cancers (e.g., volrustomig ± bevacizumab or lenvatinib; volrustomig + gemcitabine/cisplatin). RCC combinations with VEGF‑TKIs (e.g., lenvatinib/axitinib) are also in early‑phase evaluation. (mskcc.org)

Safety

Class‑consistent immune‑related adverse events (irAEs) occur and increase with higher dosing/intensity of CTLA‑4 engagement. In RCC expansion at 1,500 mg Q3W, grade 3–4 treatment‑related AEs occurred in 74.1% with discontinuations in 70.4%; hepatotoxicity was a common reason for discontinuation. In the dose‑escalation/expansion RCC cohorts overall, grade 5 TRAEs occurred in 1 patient per cohort. (ascopubs.org)
In NSCLC (ESMO 2022), volrustomig 1,500 mg + chemotherapy had grade ≥3 TRAEs and discontinuations of 70% each; lowering to 750 mg + chemotherapy reduced grade ≥3 TRAEs to 32% and discontinuations to 20%, while maintaining antitumor activity signals. (oncologypro.esmo.org)
Across first‑line RCC mini‑oral cohorts (ESMO 2023), grade 3–4 immune‑related AEs were more frequent at 750 mg than 500 mg (46.9% vs 24.2%), but most non‑endocrine irAEs resolved and about half did not require steroids; overall disease control remained high. (oncologypro.esmo.org)

HealthScout AI Analysis

Goal: Evaluate the safety and efficacy of adding the bispecific checkpoint inhibitor volrustomig to first-line FOLFIRI plus bevacizumab in metastatic colorectal cancer, using a master protocol platform to compare novel combinations against an active control.

Patients: Adults with histologically confirmed colorectal adenocarcinoma that is pMMR/MSS, metastatic, and without liver metastases, ECOG 0–1, measurable disease by RECIST 1.1, adequate organ function, and no prior systemic therapy for metastatic disease (adjuvant/neoadjuvant allowed if completed >6 months before recurrence). Key exclusions include CNS metastases, active autoimmune disease, significant cardiovascular or thromboembolic history, bleeding risks, recent GI perforation/fistula/abscess, prior immune-mediated therapy, and potentially resectable disease planned for curative surgery.

Design: Phase II, global, open-label, randomized, multicenter platform (master protocol with substudies). Approximately 120 participants will be randomized to experimental versus active-comparator arms. Stratification factors are not specified. Treatment continues until progression, unacceptable toxicity, or withdrawal. Assessments follow RECIST 1.1.

Treatments: Experimental: Volrustomig plus FOLFIRI (irinotecan, 5-FU, leucovorin) and bevacizumab. Control: FOLFIRI and bevacizumab. Volrustomig (MEDI5752) is a monovalent bispecific antibody targeting PD-1 and CTLA-4, designed to fully inhibit PD-1 and preferentially inhibit CTLA-4 on activated PD-1+ T cells within the tumor microenvironment, potentially enhancing antitumor activity while limiting peripheral toxicity. The bispecific format promotes PD-1 internalization and degradation, distinguishing it from conventional dual-antibody combinations. In phase 1 studies across solid tumors, particularly first-line RCC, volrustomig demonstrated objective response rates in the mid-40% range with dose-dependent immune-related toxicities; development focuses on doses below 1500 mg to optimize the benefit-risk profile. FOLFIRI plus bevacizumab is a standard first-line regimen for mCRC that improves response and progression-free survival versus chemotherapy alone.

Outcomes: Primary endpoints: progression-free survival by RECIST 1.1 and safety (incidence of adverse events). Key secondary endpoints: overall survival, objective response rate, disease control rate, duration of response, PFS2, pharmacokinetics (Cmax, Ctrough), and immunogenicity (anti-drug antibodies). Assessment window is approximately 3 years.

Burden on patient: Moderate to high. Participants will receive combination IV therapy with frequent infusion visits typical of FOLFIRI and bevacizumab schedules, plus additional infusion time for volrustomig in the experimental arm. Imaging per RECIST at regular intervals, serial laboratory monitoring, and safety assessments are required. The investigational agent adds pharmacokinetic and immunogenicity blood sampling, especially early in treatment, increasing chair time and venipunctures. Provision of archival or recent FFPE tumor tissue is required; new biopsy is not mandated but may be requested per site practice. Travel burden reflects biweekly chemotherapy cycles and study-specific visit schedules over many months until progression or toxicity.

Last updated: Oct 2025

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Woodville South, 5011, Australia

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Wollongong, 2500, Australia

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East Melbourne, 3002, Australia

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Victoria, British Columbia, V8R 6V5, Canada

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Barrie, Ontario, L4M 6M2, Canada

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Toronto, Ontario, M5G 1X6, Canada

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Beijing, 100142, China

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Zhengzhou, 450000, China

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Wuhan, 430079, China

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Harbin, 150081, China

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Marseille, 13273, France

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Montpellier, 34298, France

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Poitiers, 86021, France

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Saint-Priez En Jarez, 42270, France

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Villejuif, 94805, France

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Bordeaux, 33076, France

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Essen, 45147, Germany

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Roma, 00168, Italy

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Florence, 50134, Italy

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Bologna, 40133, Italy

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Milan, 20133, Italy

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Castelfranco Veneto, 31033, Italy

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Milan, 20162, Italy

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Pavia, 27100, Italy

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Pisa, 56100, Italy

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Amsterdam, 1066 CX, Netherlands

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Maastricht, 6202 AZ, Netherlands

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Zwolle, 8025 AB, Netherlands

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Seoul, 03080, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Seoul, 5505, South Korea

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Yongin-si, 16995, South Korea

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Valencia, 46010, Spain

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Barcelona, 08035, Spain

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Barcelona, 8003, Spain

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Madrid, 28007, Spain

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Madrid, 28034, Spain

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Pamplona, 31005, Spain

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Santander, 39008, Spain

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Kaohsiung City, 80756, Taiwan

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Taipei, 10002, Taiwan

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Taoyuan District, 333, Taiwan

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Yung Kang City, 71044, Taiwan

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London, W12 0HS, United Kingdom

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Manchester, M20 4GJ, United Kingdom

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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

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Cambridge, CB2 0XY, United Kingdom

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London, NW1 2PG, United Kingdom

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Scottsdale, Arizona, 85259, United States

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Los Angeles, California, 90089, United States

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Washington D.C., District of Columbia, 20007, United States

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Chicago, Illinois, 60637, United States

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Baltimore, Maryland, 21224, United States

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Boston, Massachusetts, 02114, United States

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Rochester, Minnesota, 55905, United States

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Trenton, New Jersey, 08690, United States

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Rochester, New York, 14618, United States

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Cleveland, Ohio, 44106, United States

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Portland, Oregon, 97239, United States

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Philadelphia, Pennsylvania, 19104, United States

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Nashville, Tennessee, 37232, United States

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Houston, Texas, 77030, United States

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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

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (76)

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