Study of Volrustomig as Monotherapy or in Combination With Anti- Cancer Agents in Participants With Advanced/Metastatic Solid Tumors (eVOLVE-02)

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: Cervical Cancer; Head and Neck Squamous Cell Carcinoma

Treatments: Drug: Carboplatin; Drug: Cisplatin; Biological: Volrustomig; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT06535607

D798MC00002

Details and patient eligibility

About

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.

Full description

eVOLVE-02 study will evaluate volrustomig monotherapy or volrustomig-based combination therapy in various advanced or metastatic solid tumors.

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 20 evaluable participants with head and neck squamous cell carcinoma.

In sub-study 3, Volrustomig in Combination with Chemotherapy will be evaluated in approximately 60 evaluable participants with head and neck squamous cell carcinoma.

Enrollment: 110 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

110 participants in 3 patient groups

Sub-study 1

Experimental group

Description:

Volrustomig monotherapy

Treatment:

Biological: Volrustomig

Sub-study 2

Experimental group

Description:

Volrustomig monotherapy

Treatment:

Biological: Volrustomig

Sub-study 3

Experimental group

Description:

Volrustomig in combination with carboplatin plus paclitaxel or 5-FU plus platinum

Treatment:

Drug: Paclitaxel

Biological: Volrustomig

Drug: Cisplatin

Drug: Carboplatin