Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical)

Women with locally advanced cervical cancer will be randomized in a 1:1 ratio to receive treatment with Volrustomig or Placebo.

Inclusion criteria

For inclusion in the study, patients should fulfill the following criteria:

• Female.
• Aged at least 15 years at the time of screening. Note: Participants < 18 years of age: physical changes should be aligned with Tanner Stage III.
• Body weight > 35 kg.
• Histologically documented FIGO 2018 Stage IIIA to IVA cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma, with no evidence of metastatic disease.
• Initial staging procedures performed no more than 56 days prior to the first dose of CCRT.
• Provision of FFPE tumor sample to assess the PD-L1 expression.
• Must not have progressed following CCRT, participants with persistent disease after definitive CCRT must not be amenable to other available therapies with curative intent.
• WHO/ECOG performance status of 0 or 1; duration of life expectancy of ≥ 12 weeks.
• Adequate organ and bone marrow function.
• Capable of providing signed informed consent.

Exclusion criteria

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

• Diagnosis of small cell (neuroendocrine) or mucinous adenocarcinoma of cervical cancer.
• Evidence of metastatic disease.
• Intent to administer a fertility-sparing treatment regimen.
• History of organ transplant or allogenic stem cell transplant.
• History of active primary immunodeficiency or active or prior documented autoimmune or inflammatory disorders.
• Uncontrolled intercurrent illness.
• 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; b) Adequately treated nonmelanoma skin cancer or lentigo maligna, or carcinoma in situ without evidence of disease.
• Unresolved toxicities from previous CCRT except for irreversible toxicity that is not reasonably expected to be exacerbated.
• Prior history or presence of vesicovaginal, colovaginal, or rectovaginal fistula.
• History of anaphylaxis to any biologic therapy or vaccine.
• 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); c) Physiologic doses of oral corticosteroids, ie, not exceeding 10 mg/day of prednisone (or equivalent) in the preceding 14 days.
• Patients who have undergone a previous hysterectomy, including a supracervical hysterectomy, or will have a hysterectomy as part of their initial cervical cancer therapy.
• Any prior (besides prior CCRT) or concurrent treatment for cervical cancer.
• Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
• Exposure to immune mediated therapy prior to the study for any indication.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention.
• Participants with a known allergy or hypersensitivity to the study intervention, or any excipients of the study intervention.