To assess the safety and tolerability of increasing doses of PF-07104091 and to estimate the Maximum Tolerated Dose (MTD) and/or select the Recommended Phase 2 dose (RP2D) for PF-07104091 as a single agent in participants with advanced or metastatic small cell lung, breast and ovarian cancers.
Study C4161001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-07104091 in adult patients with advanced or metastatic small cell lung cancer (SCLC), advanced platinum resistant epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer, locally recurrent/advanced or metastatic triple negative breast cancer (TNBC), HR-positive HER2-negative advanced or mBC, advanced or metastatic non-small cell lung cancer (NSCLC). This two part study will assess the safety and tolerability of increasing dose levels of PF-07104091 in Part 1, and establish the recommended Phase 2 dose (RP2D) in Part 2.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
157
PF-07104091 will be administered orally
PF-07104091 will be administered orally in combination with palbociclib and fulvestrant
PF-07104091 will be administered orally in combination with palbociclib and letrozole
Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
Clive, Iowa, 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: 28 days
To evaluate incidence of treatment emergent adverse events and laboratory abnormalities
Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities will be summarized by dose level
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Evaluate pulse rate that is out of normal range and changes in pulse rate as compared to baseline
Identify pulse rate readings that are outside the normal range. The number and percentage of participants who experienced significant pulse rate change from baseline will be summarized by dose level
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
Evaluate blood pressure that is out of normal range and changes in blood pressure as compared to baseline
Identify systolic and diastolic readings that are outside the normal range. The number and percentage of participants who experienced significant blood pressure change from baseline will be summarized by dose level
Time frame: From baseline until end of study treatment or study completion (approximately 2 years)
To evaluate heart rate corrected QT interval and changes in corrected QT interval as compared to baseline
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)
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PF-07104091 will be administered orally
PF-07104091 will be administered orally
PF-07104091 will be administered orally in combination with fulvestrant
PF-07104091 + fulvestrant (post 4/6) dose expansion
Des Moines Oncology Research Association
Des Moines, Iowa, United States
Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
Des Moines, Iowa, United States
Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
Des Moines, Iowa, United States
Norton Hospital
Louisville, Kentucky, United States
Norton Cancer Institute, St. Matthews Campus
Louisville, Kentucky, United States
Norton Cancer Institute, Audubon
Louisville, Kentucky, United States
Norton Brownsboro Hospital
Louisville, Kentucky, United States
Norton Cancer Institute, Brownsboro Campus
Louisville, Kentucky, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
...and 12 more locations
To evaluate the preliminary antitumor activity of PF-07104091 as a single agent and in combination with palbociclib and in combination with letrozole or fulvestrant or fulvestrant alone by objective response rate (ORR) in dose expansion
Percentage of participants with a best overall response of complete response (CR) or partial response (PR) using RECIST 1.1
Time frame: From baseline through disease progression or study completion (approximately 2 years)
Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose
Peak concentration of PF-07104091 during selected cycles
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Time to maximum plasma concentration (Tmax) of PF-07104091 after a single dose and multiple dose
Time to peak concentration of PF-07104091 during selected cycles
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-07104091
AUC of PF-07104091 will be calculated at selected cycles
Time frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Area under the curve of PF-07104091 with or without food
AUC of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
Maximum plasma concentration of PF-07104091 with or without food
Peak concentrations of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food
Time frame: From baseline through time to event on study or study completion (approximately 2 years)
To document any preliminary evidence of antitumor activity of PF-07104091 as a single agent and in combination with palbociclib and in combination with letrozole or fulvestrant or fulvestrant alone by objective response rate (ORR) in dose escalation
Percentage of participants with a best overall response of CR or PR using RECIST 1.1
Time frame: From baseline and every 8 weeks through disease progression or study completion (approximately 2 years)
To document any preliminary evidence of antitumor activity of PF-07104091 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)