This is an open-label, multi center study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-07248144 and early signs of clinical efficacy of PF-07248144 as a single agent and in combination with other agents
Disease Characteristics - Breast, Prostate, and Lung Cancer
Part 1A (Monotherapy Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer, CRPC, or NSCLC that is intolerant or resistant to standard therapy or for which no standard therapy is available.
Part 1B, Part 1C, Part 1D and Part 1E (Combination Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of treatment with an endocrine therapy and CDK4/6 inhibitor in the advanced or metastatic setting.
Part 2A (ER+HER2- breast cancer 2L+, monotherapy) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of CDK4/6 inhibitor and 1 line of endocrine therapy.
Unmanageable ascites (limited medical treatment to control ascites is permitted, but all participants with ascites require review by sponsor's medical monitor).
Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
Major surgery, radiation therapy, or systemic anti-cancer therapy within 3 weeks prior to study entry.
Prior irradiation to >25% of the bone marrow.
Sequential
PF-07248144
DrugKAT6 Inhibitor
Fulvestrant
DrugEndocrine Therapy
Letrozole
DrugEndocrine Therapy
Palbociclib
DrugCDK4/6 Inhibitor
PF-07220060
DrugCDK4 inhibitor
PF-07850327, ARV-471, vepdegestrant
DrugPROTAC (PROteolysis Targeting Chimera) ER degrader
10
Treatment groupsSee each treatment group below.
Number of participants with dose-limiting toxicities in the Dose Escalation Arms.
Dose-limiting toxicities (DLTs)
Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms.
Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms.
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms
Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms
Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E)
Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms
Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E)
Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms
Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E)
Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms
Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E)
