The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07220060 and PF-07104091) in people with breast cancer. This clinical study consists of 2 parts (part 1 and part 2). In part 1, we are seeking participants who: * Have been diagnosed with Breast Cancer (BC) of either types: * Have HR+, HER2- BC * Refractory HR-positive/HER2-positive BC * Have other solid tumors other than BC In part 2, we are seeking participants who: -Have HR-positive/HER2-negative BC Part 1 will include increasing doses of PF-07220060 with PF-07104091. In part 2, participants will take 1 of 2 study medicine combinations. This will help us decide the highest amount of study medicines that can be safety given to people. All participants in this study will receive PF-07220060 with PF-07104091 by mouth. We will compare participant experiences to help us determine if PF-07220060 with PF-07104091 is safe and effective. Participants will take part in this study for about 2 years. During this time, they will receive the study medicine, an x-ray imaging, and will be observed for safety and effects of the study medicines.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
192
PF-07104091 and PF-07220060 will be administered orally
PF-07104091 and PF-07220060 will be administered orally
PF-07104091 and PF-07220060 will be administered orally
PF-07104091 and PF-07220060 will be administered orally
PF-07104091 and PF-07220060 will be administered orally
PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
PF-07104091 and PF-07220060 will be administered orally in combination with letrozole
PF-07104091 and PF-07220060 will be administered orally
PF-07104091 and PF-07220060 will be administered orally
PF-07104091 and PF-07220060 will be administered orally
Administrative Address: UCLA Hematology/Oncology
Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
UCLA Hematology/Oncology
Los Angeles, California, United States
UCLA Hematology / Oncology-Parkside
Santa Monica, California, United States
UCLA Hematology/Oncology-Santa Monica
Santa Monica, California, United States
Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle
Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level
Time frame: Cycle 1 (28 days)
Number of participants with treatment emergent adverse events (AEs)
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Incidence of participants with clinical laboratory abnormalities
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Number of participants with vital signs abnormalities
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Number of participants with corrected QT (QTc) interval
Determine the effect of the drug on QT prolongation. The number and percentage of participants who experienced QT interval prolongation will be summarized by dose level
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Maximum plasma concentration (Cmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Time to maximum plasma concentration (Tmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07220060 and PF-07104091 together
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Objective response rate (ORR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
Percentage of participants with a best ORR of complete response (CR) or partial response (PR) using RECIST 1.
Time frame: From baseline through disease progression or study completion (approximately 2 years)
To evaluate the preliminary antitumor activity of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole by time to event endpoints
Time from first assessment of event endpoint to last assessment of using RECIST 1.1
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
Duration of Response (DoR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
DoR is defined as the time from first documentation of CR or PR to date of first documentation of progressive disease/pharmacodynamic (PD) or death due to any cause, whichever occurs first
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
Progression-Free Survival (PFS) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
PFS is defined as time from start date of treatment to the date of first documentation of PD or death due to any cause
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
Time to Progression (TTP) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
TTP is defined as the time from start date of treatment to the date of the first documentation of PD
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
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