Study of Volrustomig as Monotherapy or in Combination With Anti- Cancer Agents in Participants With Advanced/Metastatic Solid Tumors

Phase 2

Recruiting

• Conditions: Cervical Cancer; Head and Neck Squamous Cell Carcinoma
• Interventions: Biological: Volrustomig

• Registration Number: NCT06535607
• Lead Sponsor: AstraZeneca

Brief Summary

eVOLVE-02 study will evaluate the efficacy and safety of volrustomig as monotherapy or in combination with anti-cancer agents in participants with advanced/metastatic solid tumors.

Detailed Description

eVOLVE-02 study will evaluate volrustomig monotherapy or volrustomig-based combination therapy in various advanced or metastatic solid tumors. Data from this Phase II platform study will inform future Phase III studies.

In sub-study 1, volrustomig will be evaluated as monotherapy in approximately 30 evaluable participants with cervical cancer.

In sub-study 2, volrustomig will be evaluated as monotherapy in approximately 30 evaluable participants with head and neck squamous cell carcinoma.

Study Timeline

• Study First Submitted: 2024-07-31
• Study First Submitted QC: 2024-07-31
• Study First Posted: 2024-08-02
• Study Start: 2024-08-22
• Status Verified: 2025-02
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-06
• Primary Completion: 2026-07-30
• Study Completion: 2026-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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.

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. 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.
7. 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.
8. 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.
9. Active or prior documented autoimmune or inflammatory disorders.
10. Participants who are candidates for curative therapy.
11. Prior exposure to any immune-mediated therapy.
12. 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).
13. Receipt of the last dose of anti-cancer therapy 28 days prior to the first dose of study intervention or 5 half-lives of the respective agent, whichever is longer.
14. Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
15. 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.
16. Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
17. Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention.
18. Participants with a known allergy or hypersensitivity to the study intervention, or any excipients of the study intervention.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Volrustomig	Volrustomig	This single-arm study consists of multiple sub-studies, divided by indication.

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	Through study completion, an average of 3 years	Confirmed ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by Investigator per RECIST 1.1.
The number of participants with adverse events/serious adverse events	Through study completion, an average of 3 years	Number of participants with adverse events and with serious adverse events including abnormal clinical observations, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline.

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	Through study completion, an average of 3 years	PFS is defined as the time from date of first dose of study intervention until progression per RECIST 1.1 as assessed by Investigator or ICR, or death due to any cause.
Duration Of Response (DOR)	Through study completion, an average of 3 years	DoR is defined as the time from the date of first documented confirmed response (which is subsequently confirmed) until date of documented progression per RECIST 1.1 as assessed by Investigator or ICR, or death due to any cause.
Objective response rate (ORR) in participants with different expression levels of PD-L1	Through study completion, an average of 3 years	Confirmed ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by Investigator per RECIST 1.1 (For HNSCC sub-study 2)
Time to response (TTR)	Through study completion, an average of 3 years	TTR is defined as the time from the date of the first dose of study intervention until the date of first documented objective response, which is subsequently confirmed per RECIST 1.1, as assessed by Investigator or ICR.
Overall Survival (OS)	Through study completion, an average of 3 years	OS is defined as the time from the date of first dose of study intervention until the date of death due to any cause.
PK of volrustomig	Through study completion, an average of 2 years	Concentration of Volrustomig in serum.
The immunogenicity of volrustomig	Through study completion, an average of 3 years	Incidence of ADAs against volrustomig in serum.

Trial Locations

Locations (1)

Research Site; 🇨🇳 Wuhan, China