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 to other parts of the body
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 will test PF-08634404 with a medicine called PF-08046054/SGN-PDL1V
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.
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.
Participants with known AGAs including EGFR, ALK and ROS1, NTRK, BRAF, and MET for which there are available first-line therapies per local standard-of-care (SOC)
History of another malignancy within 2 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
Sequential
PF-08634404
Biological/Vaccine-Concentrate for solution for infusion
Sigvotatug Vedotin
Biological/Vaccine-Powder for concentrate for solution for infusion. Single use vial
PF-08046054/SGN-PDL1V
Biological/Vaccine-Powder for concentrate for solution for infusion. Single use vial.
Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
Phase I: Number of participants with dose limiting toxicity (DLT)
Dose limiting toxicity based on dose limiting toxicity evaluable participants. The number of participants who experienced DLTs during the DLT observation period.
Phase 2: Confirmed Objective Response Rate (ORR) per RECIST v1.1 by investigator
ORR is defined as the proportion of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or confirmed Partial Response (PR) per RECIST v1.1.
Phase I: Confirmed ORR per RECIST v1.1 by investigator
ORR is defined as the proportion of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or confirmed Partial Response (PR) per RECIST v1.1.
Disease Control Rate (DCR) per RECIST v1.1 by investigator
DCR by investigator assessment is defined as the proportion of participants with CR or PR with confirmation, or Stable Disease (SD) by investigator assessment per RECIST version 1.1.
Duration of Response (DOR) per RECIST v1.1 by investigator
DOR is defined as the time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurs first.
Progression Free Survival (PFS) per RECIST v1.1 by investigator
Progression-free survival is defined as the time from the date of randomization to the date of the first documentation of objective PD assessed by investigator per RECIST v1.1, or death due to any cause, whichever occurs first.
Overall Survival (OS)
Overall survival defined as the time from the date of randomization to the date of death due to any cause.
