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

Eligibility 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
• 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.