A Study of PF-08046052/SGN-EGFRd2 in Advanced Solid Tumors

Inclusion Criteria:

• Tumor types:

• For Part A: Participants must have disease that is relapsed, refractory, or beintolerant to standard of care therapies, and in the judgement of theinvestigator must have no appropriate standard therapy available at the time ofenrollment. Participants must have histologically- or cytologically confirmedmetastatic or unresectable solid malignancy from one of the following tumortypes:

• Colorectal cancer (CRC)

• Non-small cell lung cancer (NSCLC)

• Head and neck squamous cell cancer (HNSCC)-non-nasopharyngeal subtypeONLY; nasopharyngeal subtype is not eligible.

• For Part B: Participants must have disease that is relapsed, refractory, or beintolerant to standard of care therapies, and in the judgement of theinvestigator must have no appropriate standard therapy available at the time ofenrollment.

• The tumor type(s) to be enrolled in dose optimization will be identifiedby the sponsor from among those specified in Part A.

• For Part C: Participants must have disease that is relapsed or refractory or beintolerant to standard of care therapies as specified below, unlesscontraindicated:

• CRC

• Participants must have unresectable locally advanced or metastaticCRC.

• Prior therapy: Participants must have received priorfluoropyrimidine, oxaliplatin and irinotecan. Participants withdefective mismatch repair and microsatellite instability high (dMMR/MSI-H) should have received prior treatment with pembrolizumab,a nivolumab-containing regimen, or other available anti-PD-1 (programmed cell death protein 1) or anti PD L1 (programmed celldeath 1 ligand) agents.

• NSCLC

• Participants must have unresectable locally advanced or metastaticNSCLC.

• Prior therapy: Participants must have received platinum-based therapyand at least 1 PD-1/PD-L1 inhibitor. These agents may have beenadministered either as single agents or in combination. Participantswith an activating mutation or rearrangement (eg, EGFR, anaplasticlymphoma kinase [ALK], etc.) must have received available targetedagents if eligible by biomarker status and local standard of care.

• HNSCC

• Participants must have unresectable locally advanced or metastaticHNSCC - non-nasopharyngeal subtype ONLY; nasopharyngeal subtype isnot eligible.

• Prior therapy: Participants must have received platinum-based therapyand a PD-1/PD-L1 inhibitor, if eligible by biomarker status and localstandard of care. These agents may have been administered either assingle agents or in combination.

• Pancreatic ductal adenocarcinoma (PDAC)

• Participants must have unresectable locally advanced or metastaticPDAC.

• Prior therapy: Participants must have received gemcitabine- orFOLFIRINOX-based therapy.

• Participants should provide archival tumor tissue if available and also agree tobiopsies, if medically feasible

• An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

• Measurable disease at baseline per RECIST 1.1 criteria.

Exclusion Criteria:

• History of another malignancy within 3 years before the first dose of studytreatment, or any evidence of residual disease from a previously diagnosedmalignancy. Exceptions are malignancies with a negligible risk of metastasis ordeath

• Known active central nervous system metastases or leptomeningeal disease.Participants with previously treated brain metastases may participate provided theyare

• clinically stable for at least 4 weeks prior to study entry after brainmetastases treatment,

• they have no new or enlarging brain metastases,

• and are off of corticosteroids prescribed for symptoms associated with brainmetastases for at least 7 days prior to the first dose of study drug.

• Treatment with an aminobisphosphonate IV (eg ibandronate, pamidronate, zoledronate,etc.) within 4 weeks of the first dose of study treatment.

• Participants with history of thromboembolic phenomena within 6 months prior to thefirst dose of study intervention, or with contraindication to thromboembolismprophylaxis (if clinically indicated) for a previous history of thrombus.