Sponsor: AstraZeneca (industry)
Phase: 2
Start date: Aug. 22, 2024
Planned enrollment: 110
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)
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)
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)
Last updated: Sep 2026
Goal: Evaluate the antitumor activity and safety of volrustomig alone or with chemotherapy in recurrent or metastatic cervical cancer and head and neck squamous cell carcinoma (HNSCC).
Patients: Adults with measurable disease, ECOG performance status 0–1, adequate organ function, and a tumor sample available for PD-L1 assessment. The cervical cancer cohort includes patients who progressed after one or two prior systemic regimens. HNSCC cohorts include patients with incurable recurrent or metastatic disease; eligibility varies by sub-study and prior treatment status. Prior immune-mediated therapy and active autoimmune disease are exclusions.
Design: Multicenter phase II study comprising three disease- and regimen-specific sub-studies. The registry specifies randomized allocation, but the described arms do not identify a comparator or explain how randomization is applied. Approximately 30 evaluable patients are planned for cervical cancer monotherapy, 20 for HNSCC monotherapy, and 60 for HNSCC combination therapy.
Treatments: Volrustomig is given alone in the cervical cancer and one HNSCC sub-study, and with carboplatin plus paclitaxel or a platinum agent plus 5-fluorouracil in the other HNSCC sub-study. Volrustomig is an investigational bispecific antibody targeting PD-1 and CTLA-4; PD-1 binding is intended to concentrate CTLA-4 blockade on activated T cells. Earlier studies reported responses, including a 19.8% objective response rate in a heterogeneous phase I monotherapy cohort and 26.3% in a small HNSCC phase II interim cohort, but efficacy for these study populations remains uncertain. Platinum-based chemotherapy, paclitaxel, and 5-fluorouracil are established cytotoxic agents used in HNSCC regimens.
Outcomes: Primary measures are investigator-assessed confirmed objective response rate by RECIST 1.1 and the incidence of adverse and serious adverse events. Secondary measures include duration and time to response, disease control, progression-free and overall survival, survival landmarks, serum volrustomig concentrations, and anti-drug antibodies, assessed through study completion (approximately three years).
Burden on patient: Moderate to high. Treatment requires repeated clinic visits, imaging for response assessment, and blood tests for safety, pharmacokinetics, and anti-drug antibodies; a tumor sample is required for PD-L1 assessment, although whether a new biopsy is necessary is not specified. The chemotherapy cohort is likely to have greater visit and toxicity burden than the monotherapy cohorts. Visit frequency and sampling schedules are not provided.
Last updated: Sep 2026
Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.
Inclusion Criteria:
For inclusion in the study, patients should fulfill the following criteria:
1. Age ≥18 at the time of signing the ICF.
2. Provision of tumor sample to assess the PD-L1 expression.
3. Measurable disease according to RECIST 1.1.
4. ECOG performance status of 0 or 1.
5. Life expectancy ≥ 12 weeks.
6. Adequate organ and bone marrow function.
7. Body weight \> 35 kg.
8. Capable of giving signed informed consent.
9. For sub-study 1, participants with R/M cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, that: have experienced disease progression during or after treatment with standard systematic therapy per local guideline; have received at least 1 line but no more than 2 lines of prior systemic treatment regimens for R/M cervical cancer.
10. For sub-study 2, for participants with OPC must have documented HPV status.
11. For sub-study 2, participants with R/M HNSCC, that: (a) Are histologically or cytologically documented R/M HNSCC of the OP, OC, HP, and LX that is considered incurable by local therapies; (b) Participants that have not been treated in R/M setting must have: (i) a documented PD-L1 positive result, (ii) with no prior systemic anti-cancer therapy for R/M HNSCC; (c) Platinum refractory participants must have relapsed from or are refractory to the first line of prior platinum-containing regimen.
12. For sub-study 3, participants with R/M HNSCC, that: (a) Are histologically or cytologically documented R/M HNSCC of the OP, OC, HP, and LX that is considered incurable by local therapies; (b) Participants that have not been treated in R/M setting
Exclusion Criteria
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Spinal cord compression.
2. Brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention.
3. Participants with primary neuroendocrine, mesenchymal, sarcomatoid histologies, or other histologies not mentioned as part of the inclusion criteria.
4. Have not recovered (ie, ≤ Grade 1 or at baseline) from an AE due to a previously administered anti-cancer therapy.
5. For sub-study 2, have had radiotherapy within 2 weeks prior to enrollment.
6. For sub-study 3, Participants have contraindications to any of the following drugs: 5-FU, paclitaxel and carboplatin
7. History of another primary malignancy except for a) Malignancy treated with curative intent with no known active disease ≥2 years before the first dose of study intervention and of low potential risk for recurrence; b) Adequately treated nonmelanoma skin cancer or lentigo maligna, or carcinoma in situ without evidence of disease.
8. Any evidence of diseases, and/or history of organ transplant or allogenic stem cell transplant, which makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
9. Evidence of the following infections: active infection including tuberculosis; known HIV infection. that is not well controlled; active or uncontrolled HBV or HCV; or active hepatitis A.
10. Active or prior documented autoimmune or inflammatory disorders.
11. Participants who are candidates for curative therapy.
12. Prior exposure to any immune-mediated therapy.
13. Current or prior use of immunosuppressive medication within 14 days before the first dose of the study intervention is excluded. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection); b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication or chemotherapy premedication) or a single dose for palliative purpose (eg, pain control).
14. Participants are ineligible if they have received any anti-cancer therapy within 28 days prior to the first dose of study intervention or within 5 half-lives of the respective agent, whichever is longer..
15. Any concurrent chemotherapy except study intervention, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
16. Radiotherapy treatment with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.
17. Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
18. Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention.
19. Participants with a known allergy or hypersensitivity to any study intervention, on any excipients of any study intervention.
Ijuí, 98700-000, Brazil
No email / No phone
Status: Recruiting
Vitória, 29043-260, Brazil
No email / No phone
Status: Recruiting
São Caetano do Sul, 09541-270, Brazil
No email / No phone
Status: Recruiting
Londrina, 86015-520, Brazil
No email / No phone
Status: Recruiting
Shanghai, 200120, China
No email / No phone
Status: Recruiting
Shenyang, 110004, China
No email / No phone
Status: Recruiting
Tianjin, 300060, China
No email / No phone
Status: Recruiting
Wuhan, 430022, China
No email / No phone
Status: Recruiting
Wuhan, 430030, China
No email / No phone
Status: Recruiting
Wuhan, 430040, China
No email / No phone
Status: Recruiting
Wuhan, 430079, China
No email / No phone
Status: Recruiting
Wuhou District, 610041, China
No email / No phone
Status: Recruiting
Beijing, 100730, China
No email / No phone
Status: Recruiting
Beijing, CN-100730, China
No email / No phone
Status: Recruiting
Changsha, 410003, China
No email / No phone
Status: Recruiting
Changsha, 410008, China
No email / No phone
Status: Recruiting
Chengdu, 610072, China
No email / No phone
Status: Recruiting
Chongqing, 400030, China
No email / No phone
Status: Recruiting
Dongguan, 523009, China
No email / No phone
Status: Recruiting
Hangzhou, 310022, China
No email / No phone
Status: Recruiting
Jining, 272029, China
No email / No phone
Status: Recruiting
Kunming, 650118, China
No email / No phone
Status: Recruiting
Nanchang, 330006, China
No email / No phone
Status: Recruiting
Nanning, 530021, China
No email / No phone
Status: Recruiting
Shandong, 250117, China
No email / No phone
Status: Recruiting
Shandong, China
No email / No phone
Status: Recruiting
Namdong-gu, 21565, South Korea
No email / No phone
Status: Recruiting
Seoul, 03722, South Korea
No email / No phone
Status: Recruiting
Taipei, 112, Taiwan
No email / No phone
Status: Recruiting
Ho Chi Minh City, 700000, Vietnam
No email / No phone
Status: Recruiting
Hanoi, 100000, Vietnam
No email / No phone
Status: Recruiting
Tianjin, 300060, China
No email / No phone
Status: Active, not recruiting
Wuhan, 430022, China
No email / No phone
Status: Active, not recruiting
Beijing, 100730, China
No email / No phone
Status: Active, not recruiting
Changsha, 410008, China
No email / No phone
Status: Active, not recruiting
Chengdu, 610041, China
No email / No phone
Status: Active, not recruiting
Dongguan, 523009, China
No email / No phone
Status: Active, not recruiting
Hangzhou, 310022, China
No email / No phone
Status: Active, not recruiting
Nanning, 530021, China
No email / No phone
Status: Active, not recruiting
Shandong, China
No email / No phone
Status: Active, not recruiting
Shanghai, 200120, China
No email / No phone
Status: Active, not recruiting
Zhengzhou, 450008, China
No email / No phone
Status: Not yet recruiting
Anyang, 455000, China
No email / No phone
Status: Not yet recruiting
Beijing, 100142, China
No email / No phone
Status: Not yet recruiting
Changchun, 130021, China
No email / No phone
Status: Not yet recruiting
Fuzhou, 350014, China
No email / No phone
Status: Not yet recruiting
Nanjing, 210009, China
No email / No phone
Status: Not yet recruiting
Shandong, China
No email / No phone
Status: Not yet recruiting
Taichung, Taiwan
No email / No phone
Status: Not yet recruiting
Baltimore, Maryland, 21201, United States
No email / No phone
Status: Not yet recruiting
Stony Brook, New York, 11794, United States
No email / No phone
Status: Not yet recruiting
Columbus, Ohio, 43210, United States
No email / No phone
Status: Not yet recruiting
Changsha, 410013, China
No email / No phone
Status: Completed
Fuzhou, 350011, China
No email / No phone
Status: Completed
Bengbu, 233004, China
No email / No phone
Status: Withdrawn
Changchun, 130021, China
No email / No phone
Status: Withdrawn
Chongqing, 400030, China
No email / No phone
Status: Withdrawn
Hefei, 230031, China
No email / No phone
Status: Withdrawn
Los Angeles, California, 90025, United States
No email / No phone
Status: Withdrawn