Symbiotic-Lung-20: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers

AN INTERVENTIONAL OPEN-LABEL PHASE 1B/2 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PRELIMINARY EFFICACY OF PF-08634404 IN COMBINATION WITH DIFFERENT ANTICANCER AGENTS IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

This study is being done to learn more about a new medicine called PF-08634404 and how it works when used with other cancer medicines in people who have advanced solid tumors. An advanced solid tumor is a type of cancer that has spread beyond its original location and cannot be removed by surgery or cured with standard treatments.

To join in the study, participants must:

• Be 18 years or older
• Participants with advanced non-small cell lung cancer (NSCLC), a type of lung cancer that has spread

The study will look at:

• Whether PF-08634404 is safe to use with other cancer medicines.
• What side effects may happen. A side effect is anything the medicine does to your body that is not part of treating your disease.
• Whether the combination of PF-08634404 and other cancer medicines can help treat solid tumors.

The study has different parts, each testing PF-08634404 with a different cancer medicine:

• Part A will test PF-08634404 with a medicine called sigvotatug vedotin.
• Part B of the study will look at how well the new medicine PF-08634404 works when used together with another medicine.

Participants will receive the study medicines through an intravenous (IV) infusion (injected into the vein) at the study clinic. All treatments will take place at clinical trial sites, where trained medical staff will monitor participants during and after each visit.

Inclusion Criteria:

• Pathologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous or non-squamous NSCLC and are not a candidate for complete surgical resection and curative concurrent/sequential chemoradiotherapy
• PD-L1 status available
• Part B only: PD-L1 ≥ TPS 1%
• Measurable disease based on RECIST v1.1 per investigator.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Adequate organ function

Exclusion Criteria:

• Participants with known AGAs including EGFR, ALK and ROS1, NTRK, BRAF, and MET
• History of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy
• Known active CNS lesions, including brainstem, meningeal, or spinal cord metastases or compression
• Leptomeningeal disease
• Active autoimmune diseases requiring systemic treatment within the past 2 years
• Previous systemic anti-tumor therapy for locally advanced, unresectable, or metastatic NSCLC
• Previous treatment with immunotherapy (exception is (neo)adjuvant anti-PD-(L)1), ADCs containing MMAE payload, systemic anti-angiogenic therapy, or prior radiotherapy to the lung within 6 months of first dose of study intervention