Purpose of this study is to assess the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of volrustomig in combination with other anticancer drugs in participants with specified solid tumors.

This Phase II, platform, open-label, multicenter study will evaluate the efficacy, safety, and tolerability of volrustomig in combination with anticancer drugs in various solid tumor types.

This platform study currently includes 2 substudies:

Substudy 1: metastatic non-small cell lung cancer (mNSCLC) (non-squamous [NSQ]). Participants will be randomized in two treatment arms: Arm 1A and Arm 1B.

Substudy 2: mNSCLC (squamous [SQ] or NSQ). Participants will enroll to the Arm 2A only.

All arms will test a volrustomig dosing in combination with chemotherapy.

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration.
• Life expectancy greater than or equal to (>=) 12 weeks.
• Adequate organ and bone marrow function.
• Body weight greater than (>) 35 kilograms (kg) at screening and at randomization.
• Histologically or cytologically documented NSQ NSCLC in substudy 1 and SQ or NSQ mNSCLC in substudy 2.
• Absence of sensitizing epidermal growth factor receptor (EGFR) mutations.
• Absence of documented tumor genomic alteration results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted 1L therapies.
• At least one measurable lesion not previously irradiated that can be accurately measured at baseline as >= 10 millimeter (mm) in the longest diameter.

Key Exclusion Criteria:

• Spinal cord compression.
• History of primary active immunodeficiency.
• Active or prior documented autoimmune or inflammatory disorders.
• Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant.
• Brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of radiation therapy and study enrollment.
• Prior chemotherapy or any other systemic therapy for Stage IV NSCLC. Participants who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for local disease are eligible, provided that progression has occurred greater (>) 12 months from end of last therapy.

Qualified researchers can request access to anonymized individual patient-leveldata from AstraZeneca group of companies sponsored clinical trials via therequest portal Vivli.org. All requests will be evaluated as per the AZ disclosurecommitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes",indicates that AZ are accepting requests for IPD, but this does not mean allrequests will be approved.

AstraZeneca will meet or exceed data availability as per the commitment smade to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment athttps://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure researchenvironmentVivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.