A Clinical Trial of PF-08046037 Alone or With Sasanlimab in Patients With Advanced or Metastatic Malignancies

This study is seeking participants who have the following tumor types and can provide tumor tissue samples as per below. 1. Tumor types * Monotherapy Dose Escalation (Part 1a) and Optimization (Part 2a) cohorts * Advanced or metastatic NSCLC, HNSCC, melanoma, or PDAC * Must have progressive disease following at least 1 prior approved systemic therapy * Monotherapy Dose Expansion (Part 3a) • Advanced or metastatic NSCLC or PDAC * Combination Safety Evaluation (Part 1b) and Dose Optimization (Part 2b) * Advanced or metastatic NSCLC or HNSCC * May be either a) not received prior immunotherapy for the tumor type OR b) relapse/ refractory after prior immunotherapy * Combination Dose Expansion (Part 3b) * Unresectable locally advanced or metastatic HNSCC or NSCLC * Must not have received prior systemic cytotoxic therapy in the locally advanced or metastatic setting (first-line setting) * Must be treatment naïve to any immunotherapy * NSCLC must have PD-L1 expression TPS \>=50% * HNSCC must have PD-L1 expression CPS \>=1 2. Tissue requirement * Part 1 at lower doses: sufficient archival tissue collected within 12 months of enrollment for submission to central laboratory * Part 1 at higher doses: de novo baseline tumor biopsy or archival tissue within 12 months of enrollment * Part 1 backfill: de novo baseline and on-treatment tumor biopsies are required * Part 2 and 3: de novo baseline or archival tissue within 6 months of enrollment * Part 2 and 3: mandatory on-treatment tumor biopsy, if required by sponsor 3. Measurable disease per RECIST v1.1 Participants who meet the following might not be able to participate. 1. History of Grade \>=3 immune mediated AE related to prior immune modulatory therapy and required immunosuppressive therapy 2. Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent 3. History of uveitis within the preceding 6 months 4. Clinically significant Grade \>=3 neurodegenerative disease 5. Grade 3 or higher pulmonary disease unrelated to underlying malignancy 6. Previous exposure to an investigational immunostimulatory antibody conjugate or systemic TLR agonist