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

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 notrequiring steroids for at least 14 days prior to start of study intervention. Forsub-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 inclusioncriteria.

• Have not recovered (ie, ≤ Grade 1 or at baseline) from an AE due to a previouslyadministered 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 followingdrugs: 5-FU, paclitaxel and carboplatin

• History of another primary malignancy except for a) Malignancy treated with curativeintent with no known active disease ≥2 years before the first dose of studyintervention and of low potential risk for recurrence; b) Adequately treatednonmelanoma skin cancer or lentigo maligna, or carcinoma in situ without evidence ofdisease.

• Any evidence of diseases, and/or history of organ transplant or allogenic stem celltransplant, which makes it undesirable for the participant to participate in thestudy or that would jeopardize compliance with the protocol.

• Evidence of the following infections: active infection including tuberculosis; knownHIV infection. that is not well controlled; active or uncontrolled HBV or HCV; oractive hepatitis A.

• History of active primary immunodeficiency or active or prior documented autoimmuneor 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 firstdose of the study intervention is excluded. The following are exceptions to thiscriterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection); b) Steroids as premedication for hypersensitivityreactions (eg, CT scan premedication or chemotherapy premedication) or a single dosefor palliative purpose (eg, pain control).

• For sub-study 1,2,3,4, participants are ineligible if they have received anyanti-cancer therapy within 28 days prior to the first dose of study intervention orwithin 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 thebone 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 studyintervention or still recovering from prior surgery.

• Receipt of live attenuated vaccine within 30 days prior to the first dose of thestudy intervention.

• Participants with a known allergy or hypersensitivity to any study intervention, onany excipients of any study intervention.

• For substudy 5: Participants with any prior systemic therapy, non-palliativeradiotherapy, radical pleuropneumonectomy for pleural mesothelioma.