A Study to Learn About the Study Medicine Called PF-08046032 in People With Advanced Cancers

An Open-Label Phase 1 Study to Evaluate PF-08046032 as Monotherapy and Part of Combination Therapy in Participants With Advanced Malignancies

The purpose of this study is to learn about the effects of a new study medicine called PF-08046032, when taken alone and when taken with another medicine called sasanlimab, for the treatment of advanced cancers. The effects are studied in adult participants with certain types of lymphomas or solid tumors that are advanced or metastatic (spread to other parts of the body).

The study has three parts:

• Part A will test PF-08046032 alone at increasing dose levels in participants with certain lymphomas (cancer that begins in cells of the immune system) and in participants with certain solid tumors whose disease has worsened on or after standard treatments.
• Part B will test PF-08046032 (at selected doses) and sasanlimab in participants with certain solid tumors, including those whose disease has worsened on or after standard treatments as well as participants before receiving standard treatments.
• Part C will further test the combination of PF-08046032 and sasanlimab in participants with specific types of solid tumors based on the results from Part A and Part B of the study.

All participants will receive the study drug PF-08046032. Only participants in Part B and Part C of the study will also receive sasanlimab. PF-08046032 will be given as an intravenous (IV) infusion, which means it will be injected directly into a vein. Sasanlimab will be given as a subcutaneous injection, which means it will be injected under the skin.

INCLUSION CRITERIA:

1. Histological or cytological diagnosis of metastatic or unresectable malignancy:

   • Part A1: Participants with lymphomas (cHL, PTCL, large B-cell lymphoma) who have progressed on/after standard therapies
   • Part A2: Participants with solid tumors (NSCLC, HNSCC, melanoma, or other limited tumor types) who have progressed on or following prior immune checkpoint inhibitor if indicated and available
   • Part B: Participants with solid tumors who have either progressed on/after prior immune checkpoint inhibitor, or who have not received prior immune checkpoint inhibitor therapy
   • Part C: Participants with selected tumor type who have not received systemic anticancer treatment for the tumor type (including prior immune checkpoint inhibitor

2. Measurable disease as defined by Lugano Classification for lymphomas or RECIST 1.1 for solid tumors

3. Able to provide tumor tissue(s) as defined by the protocol depending on the Part of the study at enrollment

4. ECOG Performance Status score 0 or 1

EXCLUSION CRITERIA:

1. Ongoing peripheral neuropathy
2. History of significant immune-mediated adverse event considered related to prior immune-modulatory therapy
3. Known or suspected active autoimmune disease