The purpose of this study is to understand if PF-08046054 alone works well compared to standard-of-care docetaxel alone in participants with non-small cell lung cancer (NSCLC) with PD-L1 expression greater than or equal to 1% and had cancer progression during or after treatment with PD-L1 or PD-1 inhibitors, platinum-based chemotherapy, and targeted treatment regimen(s) for participants with known actionable genomic alterations (AGAs). Participants in this study must have cancer that has spread through their body or can't be removed with surgery or treated with definitive radiation.
Participants will randomly (like a flip of the coin) be assigned to either the PF-08046054 treatment group or the docetaxel treatment group. Participants in the PF-08046054 treatment group will receive an IV infusion (injected directly into the veins) twice during each 21-day cycle. Participants in the docetaxel treatment group will receive an IV infusion once during each 21-day cycle. Study participation may be up to 5 years if the participant's NSCLC is responding to treatment. The study team will see how each participant is doing with the study treatment during regular visits at the clinic.
Histologically or cytologically confirmed diagnosis of NSCLC with locally advanced, unresectable Stage IIIB or IIIC not eligible for definitive chemoradiotherapy or metastatic (Stage IV: M1a, M1b, or M1c) disease per the American Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Union for International Cancer Control (UICC) Staging System. Note: Participants with a neuroendocrine component or histology are not eligible.
PD-L1 expression on ≥1% of tumor cells based on local immunohistochemistry (IHC) testing with an assay utilizing the anti-PD-L1 monoclonal antibody clones 22C3 or SP263.
Participants who have NSCLC with known AGAs are permitted.
Archival specimen (preferably collected within 12 months after the last anticancer therapy) (see laboratory manual for details); or
History of another malignancy within 3 years before the first dose of PF-08046054, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] ≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
The participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least >14 days prior to randomization (if requiring steroid treatment).
No clinical or radiographic progression in the CNS following CNS-directed definitive radiotherapy and/or surgery.
Time since CNS-directed treatment is ≥28 days prior to randomization.
Parallel
PF-08046054
DrugAntibody Drug Conjugate Participants will receive PF-08046054, administered as an IV infusion.
Docetaxel monotherapy
DrugParticipants will receive Docetaxel, administered as an IV infusion.
Overall Survival
Overall survival defined as the time from the date of randomization to the date of death due to any cause.
Progression Free Survival (PFS) assessed by blinded independent central review (BICR)
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 BICR per RECIST v1.1, or death due to any cause, whichever occurs first.
Objective Response Rate as assessed by BICR
The proportion of participants who have a confirmed CR or PR, as best overall response assessed by BICR as per RECIST 1.1.
Progression Free Survival as assessed by Investigator
Progression Free Survival (PFS) 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.
Objective Response Rate (ORR) as assessed by Investigator
The proportion of participants who have a confirmed CR or PR, as best overall response assessed by investigator as per RECIST 1.1.
