Investigational Drug
Volrustomig
TrialFetch AI Analysis
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Overview
Volrustomig (MEDI5752/MEDI-5752) is an investigational, humanized IgG1 bispecific antibody designed to inhibit both PD-1 and CTLA-4. It is being evaluated alone and in combination regimens across several solid tumors. Early-phase studies have shown antitumor activity, but results vary by tumor type and dose, and efficacy remains unconfirmed in successful randomized phase III trials. (pmc.ncbi.nlm.nih.gov)
In August 2026, the 895-patient phase III eVOLVE-Lung02 trial in first-line metastatic non-small cell lung cancer (NSCLC) was discontinued after an independent monitoring committee concluded that volrustomig plus chemotherapy was unlikely to improve progression-free or overall survival over pembrolizumab plus chemotherapy in the primary PD-L1-negative population. Detailed results have not yet been published. Other phase III studies in cervical cancer, head and neck squamous cell carcinoma (HNSCC), and mesothelioma are continuing. (astrazeneca.com)
Mechanism of action
Volrustomig uses PD-1 binding to concentrate CTLA-4 blockade on activated, PD-1-positive T cells. This design is intended to provide sustained PD-1 inhibition while preferentially inhibiting CTLA-4 on activated rather than resting peripheral T cells, potentially limiting systemic CTLA-4-related toxicity. Pharmacodynamic studies have demonstrated peripheral and intratumoral T-cell proliferation and activation. (aacrjournals.org)
Efficacy
- Advanced solid tumors, phase I: Among 86 patients receiving monotherapy across multiple tumor types and doses, the objective response rate (ORR) was 19.8%, including 2.3% complete responses; disease control rate was 53.5%. Median duration of response was 17.5 months, median progression-free survival (PFS) 3.7 months, and median overall survival 19.2 months. The heterogeneous population and nonrandomized design limit interpretation. (doi.org)
- First-line advanced clear-cell renal cell carcinoma, phase I expansion: ORRs were 46.9% with 750 mg and 45.5% with 500 mg every three weeks. Complete-response rates were 9.4% and 6.1%, respectively; median PFS was 11.1 and 9.9 months. (annalsofoncology.org)
- Recurrent/metastatic HNSCC, phase II interim analysis: Among 19 patients with PD-L1 combined positive score ≥1, five partial responses produced a confirmed ORR of 26.3% and disease-control rate of 52.6%. Follow-up was short at 5.4 months. (ascopubs.org)
- Metastatic NSCLC, phase III: eVOLVE-Lung02 was stopped for futility; the regimen was considered unlikely to meet its PFS or overall-survival endpoints versus pembrolizumab plus chemotherapy in patients with PD-L1-negative tumors. Numerical efficacy results have not been released. (astrazeneca.com)
Safety
In the 86-patient phase I monotherapy study, 84.9% experienced treatment-related adverse events (TRAEs), including 38.4% with grade 3–4 events. Common TRAEs included pruritus (30.2%), hypothyroidism (26.7%), hyperthyroidism (24.4%), rash (24.4%), and elevated AST (18.6%). TRAEs caused treatment discontinuation in 33.7%, and one treatment-related death was reported. Hepatic toxicity and discontinuations were more frequent at doses of 1,500 mg or higher, indicating dose-dependent tolerability. (pmc.ncbi.nlm.nih.gov)
In the small HNSCC phase II analysis, grade 3–4 treatment-related events occurred in 8.7% of patients; no patient discontinued because of an adverse event. (ascopubs.org)
Further reading
- First-in-human phase I study in Clinical Cancer Research
- Preclinical design and mechanism in Cancer Discovery
- Clear-cell renal cell carcinoma results at ESMO 2023
- Phase II HNSCC interim analysis at ASCO 2026
- August 2026 update on the phase III eVOLVE-Lung02 trial
Last updated: Sep 2026
Active trials using Volrustomig
Found 9 active trials using this drug:
TrialFetch AI summary: Adults with previously untreated, measurable pMMR/MSS metastatic colorectal adenocarcinoma without liver metastases are randomized to first-line FOLFIRI plus bevacizumab with or without volrustomig. Volrustomig is an investigational bispecific antibody targeting PD-1 and CTLA-4.
ClinicalTrials.gov ID: NCT06792695
TrialFetch AI summary: Adults with previously untreated stage IV nonsquamous NSCLC, ECOG 0–1, and no actionable driver with an approved first-line targeted therapy receive a priming dose of volrustomig, an investigational PD-1/CTLA-4 bispecific antibody, followed by one of two volrustomig dosing regimens with carboplatin and pemetrexed. There is no standard-of-care comparator arm.
ClinicalTrials.gov ID: NCT06448754
TrialFetch AI summary: Adults with recurrent or metastatic cervical cancer after 1–2 prior systemic regimens, or incurable recurrent or metastatic head and neck squamous cell carcinoma, receive volrustomig alone or, in one head and neck cohort, with platinum-based chemotherapy. Volrustomig is an investigational bispecific antibody targeting PD-1 and CTLA-4.
ClinicalTrials.gov ID: NCT06535607
TrialFetch AI summary: Adults with measurable, advanced unresectable pleural mesothelioma and ECOG performance status 0–1 are randomized to carboplatin/pemetrexed plus volrustomig, an investigational PD-1/CTLA-4 bispecific antibody, or histology-based standard care. The comparator is platinum/pemetrexed or nivolumab/ipilimumab for epithelioid disease and nivolumab/ipilimumab for non-epithelioid disease.
ClinicalTrials.gov ID: NCT06097728
TrialFetch AI summary: Adults with locally advanced or metastatic hepatocellular carcinoma receive the investigational PD-1/CTLA-4 bispecific antibody volrustomig alone or in combinations with bevacizumab, lenvatinib, or the investigational PD-1/TIGIT bispecific antibody rilvegostomig; a separate cohort receives rilvegostomig plus bevacizumab. Adults with previously untreated advanced or metastatic biliary tract cancer receive either bispecific antibody with gemcitabine and cisplatin.
ClinicalTrials.gov ID: NCT05775159
TrialFetch AI summary: Adults with previously untreated, HER2-negative, unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma receive first-line combinations of chemotherapy with volrustomig (PD-1/CTLA-4), rilvegostomig (PD-1/TIGIT), or AZD7789 (PD-1/TIM-3), all investigational bispecific antibodies. Selected substudies instead pair one of these antibodies with the CLDN18.2-directed antibody–drug conjugate AZD0901 and fluoropyrimidine chemotherapy; these substudies require central CLDN18.2 testing.
ClinicalTrials.gov ID: NCT05702229
TrialFetch AI summary: Adults with advanced or metastatic endometrial, gastric, castration-resistant prostate, ovarian, colorectal, urothelial, or biliary tract cancer receive datopotamab deruxtecan, a TROP2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor, either alone or in tumor-specific combinations. Combination partners include fluoropyrimidines, platinum chemotherapy, bevacizumab, corticosteroids, or the investigational bispecific antibodies volrustomig (PD-1/CTLA-4) and rilvegostomig (PD-1/TIGIT).
ClinicalTrials.gov ID: NCT05489211
TrialFetch AI summary: This study enrolls patients with HER2-overexpressing, unresectable locally advanced or metastatic non-squamous NSCLC and ECOG performance status 0–1; current cohorts require no prior systemic therapy for advanced disease and exclude tumors with actionable drivers that have approved treatments. Patients receive trastuzumab deruxtecan, a HER2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor, with either volrustomig (PD-1/CTLA-4 bispecific) or rilvegostomig (PD-1/TIGIT bispecific), with or without carboplatin.
ClinicalTrials.gov ID: NCT04686305
TrialFetch AI summary: Adults with unresectable locally advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma are eligible after progression on trastuzumab if HER2-positive, or in the first-line setting if HER2-positive or HER2-low, depending on the arm. Treatment includes trastuzumab deruxtecan, a HER2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor, alone or with chemotherapy and/or checkpoint inhibitors, including the investigational PD-1/CTLA-4 bispecific volrustomig or PD-1/TIGIT bispecific rilvegostomig; one arm uses trastuzumab-based chemotherapy as a comparator.
ClinicalTrials.gov ID: NCT04379596
