Overview

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.

Eligibility

Inclusion Criteria:

• Age ≥18 at the time of signing the ICF.
• Provision of tumor sample to assess the PD-L1 expression (if applicable).
• ECOG performance status of 0 or 1.
• Measurable disease according to RECIST 1.1 (variations of RECIST 1.1 if applicable).
• Life expectancy ≥ 12 weeks.
• Adequate organ and bone marrow function.
• Body weight \> 35 kg
• Capable of giving signed informed consent.

Exclusion Criteria:

• Spinal cord compression.
• For sub-study 1,2,3,4, brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention. For sub-study 5, participants with untreated or progressive brain metastases.
• For sub-study 1,2,3, participants with primary neuroendocrine, mesenchymal, sarcomatoid histologies, or other histologies not mentioned as part of the inclusion criteria.
• Have not recovered (ie, ≤ Grade 1 or at baseline) from an AE due to a previously administered anti-cancer therapy.
• For sub-study 2, have had radiotherapy within 2 weeks prior to enrollment.
• For sub-study 3,4, participants have contraindications to any of the following drugs: 5-FU, paclitaxel and carboplatin
• 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.
• 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.
• 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.
• History of active primary immunodeficiency or active or prior documented autoimmune or inflammatory disorders.
• Participants who are candidates for curative therapy.
• Prior exposure to any immune-mediated therapy.
• 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).
• For sub-study 1,2,3,4, 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.
• Any concurrent chemotherapy except study intervention, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
• 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.
• Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
• 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 any study intervention, on any excipients of any study intervention.
• For substudy 5: Participants with any prior systemic therapy, non-palliative radiotherapy, radical pleuropneumonectomy for pleural mesothelioma.