Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
- Conditions
- LiposarcomaAdenocarcinoma of LungProstate CancerBreast Neoplasms
- Interventions
- Combination Product: LetrozoleCombination Product: EnzalutamideCombination Product: Fulvestrant
- Registration Number
- NCT04557449
- Lead Sponsor
- Pfizer
- Brief Summary
This is a Phase 1/2A, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060 administered as a single agent and then in combination with endocrine therapy.
The study consists of two parts and a China and Japan monotherapy cohort. Part 1 includes dose escalation cohorts evaluating PF-07220060 as single agent or in combination with endocrine therapy or enzalutamide, as well as a food effect cohort and a DDI cohort Part 2 includes dose expansion cohorts evaluating PF-07220060 in combination with endocrine therapy or enzalutamide.
In Part 1A, single escalating doses of PF-07220060 alone will be administered to determine the maximum tolerated dose (MTD) and select the recommended dose for expansion In Part 1B and Part 1C, PF-07220060 will be administered in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively).
In Part 1D, food effect assessment of PF-07220060 at the RP2D dose level from the Part 1A will be conducted In Part 1E, the effect of PF-07220060 on the PK of midazolam will be evaluated (DDI) In Part 1F, escalating dosed of PF-07220060 will be administered in combination with enzalutamide Part 1B and Part 1C may commence at MTD or before reaching the MTD at a dose level in Part 1A.
Part 2A is a dose expansion cohort with fulvestrant and will explore more than one dose of PF-07220060 in participants diagnosed with mBC.
Part 2B and Part 2C are expansion for combination therapy of PF-07220060 with letrozole and fulvestrant, respectively.
Part 2D is the expansion cohort for combination therapy of PF-07220060 with enzalutamide.
Part 2E is an expansion cohort to evaluate PF-07220060 Monotherapy versus PF-07220060 plus fulvestrant combination therapy. The China monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as single agent in Chinese participants.
The Japan monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as a single agent in Japanese participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 337
Not provided
- Part 1D: participants who have had a gastrectomy or have dietary or other restrictions that preclude a 10 hour overnight fast or consumption of the high fat, high calorie meal
- Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor
- Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway
- Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease
- Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
- Major surgery or radiation within 4 weeks prior to study intervention
- Last anti-cancer treatment within 2 weeks prior to study intervention
- Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
- Pregnant or breastfeeding female participant
- Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 1A Monotherapy Escalation Arm 2 PF-07220060 PF-07220060 Monotherapy Escalation 1A Monotherapy Escalation Arm 4 PF-07220060 PF-07220060 Monotherapy Escalation 1B Combination Dose Finding Arm 1 Letrozole PF-07220060 with Letrozole combination Escalation 1D Monotherapy Food Effect PF-07220060 PF-07220060 Monotherapy Food Effect 1C Combination Dose Finding Arm 2 PF-07220060 PF-07220060 with Fulvestrant Combination Escalation 2D Combination Dose Expansion Enzalutamide PF-07220060 with enzalutamide Combination Expansion 2A Combination Dose Expansion Fulvestrant PF-07220060 with fulvestrant combination dose expansion 1A Monotherapy Escalation Arm 1 PF-07220060 PF-07220060 Monotherapy Escalation 1C Combination Dose Finding Arm 1 Fulvestrant PF-07220060 with Fulvestrant Combination Escalation 1C Combination Dose Finding Arm 2 Fulvestrant PF-07220060 with Fulvestrant Combination Escalation 1F Combination Dose Finding Enzalutamide PF-07220060 with Enzalutamide Escalation 1A Monotherapy Escalation Arm 3 PF-07220060 PF-07220060 Monotherapy Escalation 1B Combination Dose Finding Arm 2 PF-07220060 PF-07220060 with Letrozole Combination Escalation 1B Combination Dose Finding Arm 2 Letrozole PF-07220060 with Letrozole Combination Escalation 1C Combination Dose Finding Arm 1 PF-07220060 PF-07220060 with Fulvestrant Combination Escalation 2B Combination Dose Expansion Letrozole PF-07220060 with Letrozole Combination Expansion 2C Combination Dose Expansion PF-07220060 PF-07220060 with fulvestrant Combination Expansion 2C Combination Dose Expansion Fulvestrant PF-07220060 with fulvestrant Combination Expansion 1B Combination Dose Finding Arm 1 PF-07220060 PF-07220060 with Letrozole combination Escalation 1A Monotherapy Escalation Arm 5 PF-07220060 PF-07220060 Monotherapy Escalation 1F Combination Dose Finding PF-07220060 PF-07220060 with Enzalutamide Escalation 2D Combination Dose Expansion PF-07220060 PF-07220060 with enzalutamide Combination Expansion 2A Combination Dose Expansion PF-07220060 PF-07220060 with fulvestrant combination dose expansion 2E Combination Dose Expansion PF-07220060 PF-07220060 Monotherapy OR PF-07220060 plus fulvestrant combination therapy 2E Combination Dose Expansion Fulvestrant PF-07220060 Monotherapy OR PF-07220060 plus fulvestrant combination therapy 2B Combination Dose Expansion PF-07220060 PF-07220060 with Letrozole Combination Expansion 1E DDI Cohort PF-07220060 PF-07220060 DDI with Midazolam 1E DDI Cohort Midazolam PF-07220060 DDI with Midazolam
- Primary Outcome Measures
Name Time Method Incidence of clinically significant AEs Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days Adverse Events
DDI D1 to the end of Cycle 1 Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1E)
Number of participants with dose limiting toxicities in the Dose Escalation Portion Baseline up to day 28 of Cycle 1. First cycle (28 days) dose limiting toxicities (Parts 1A, 1B, 1C, 1F)
Incidence of clinically significant abnormal vital and ECG parameters Day 1, Day 8, Day 15 of Cycle 1 and starting from Cycle 2, and then every 28 days through study completion, up to approximately 24 months (Each cycle is 28 days) vital signs and heart rate corrected QT interval
Incidence of clinically significant laboratory assessments Weekly during Cycle 1 and 2 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months safety laboratory abnormalities
Food Effect Day -7 through the end of Cycle 1 Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1D)
- Secondary Outcome Measures
Name Time Method Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Tumor Response per RECIST v1.1 and per PCGW3 baseline up to approximately 24 months Per RECIST v1.1 (Part 1 A-E; Part 2B and 2C); per PCWG3 (Part 1F and Part 2D)
Clinical Benefit Rate (CBR) baseline up to approximately 24 months CBR per RECIST v1.1 (Parts 2B, 2C)
Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Radiographic Progression Free survival Cycle 1 (each cycle is 28 days) up to approximately 24 months Part 2D
PSA50 Cycle 1 (each cycle is 28 days) to up to approximately 24 months Part 1F and 2D
Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point Within the Dose Interval (AUClast) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Duration of Response (DOR) baseline up to approximately 24 months Per RECIST v1.1
Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero Extrapolated to Infinity (AUCinf) in the Dose Escalation and Dose Finding portion Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)
Time to Progression (TTP) baseline up to approximately 24 months TTP per RECIST v1.1
Time to first skeletal events Cycle 1 (each cycle is 28 days) to up to approximately 24 months Time to first skeletal events (Part 2D)
Progression Free Survival (PFS) baseline up to approximately 24 months PFS per RECIST v.1.1
Peak and Trough Concentration of PF-07220060 Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Peak and trough concentration (Parts 2B, 2C, 2D)
Peak and trough concentrations of enzalutamide and N-desmethyl enzalutamide Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months Peak and trough concentrations (Part 2D)
Quality of life questionnaire Cycle 1 (each cycle is 28 days) to up to approximately 24 months time to functional status deterioration by FACT-P (Part 2D)
Trial Locations
- Locations (38)
Narodny onkologicky ustav
🇸🇰Bratislava, Slovakia
Fakultna nemocnica s poliklinikou Nove Zamky
🇸🇰Nove Zamky, Slovakia
POKO Poprad, s.r.o.
🇸🇰Poprad, Slovakia
Ellison Institute
🇺🇸Los Angeles, California, United States
Smilow Cancer Hospital at Yale - New Haven
🇺🇸New Haven, Connecticut, United States
Yale-New Haven Hospital-Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Smilow Cancer Hospital Phase 1 Unit
🇺🇸New Haven, Connecticut, United States
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute- Chestnut Hill
🇺🇸Newton, Massachusetts, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Sarah Cannon Research Institute - Pharmacy
🇺🇸Nashville, Tennessee, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Hospital Británico de Buenos Aires
🇦🇷Ciudad autónoma de Buenos Aires, Buenos Aires, Argentina
Fundación Cenit Para La Investigación En Neurociencias
🇦🇷Caba, Ciudad Autã³noma DE Buenos Aires, Argentina
Fundación Respirar
🇦🇷Buenos Aires, Argentina
Clínica Universitaria Reina Fabiola
🇦🇷Córdoba, Argentina
Fundación CORI para la Investigación y Prevención del Cáncer
🇦🇷La Rioja, Argentina
Cancer Hospital Chinese Academy of Medical Science
🇨🇳Beijing, Beijing, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
INCAN
🇲🇽Cdmx, Distrito Federal, Mexico
Hospital MAC Periferico Sur
🇲🇽Ciudad de Mexico, Distrito Federal, Mexico
COI Centro Oncologico Internacional S.A.P.I. de C.V.
🇲🇽Mexico City, Distrito Federal, Mexico
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
🇲🇽Monterrey, Nuevo LEÓN, Mexico
Hospital Reforma
🇲🇽Oaxaca de Juárez, Oaxaca, Mexico
Oaxaca Site Management Organization
🇲🇽Oaxaca, Mexico
Onkologicky ustav sv. Alzbety, s.r.o., Interna klinika VSZaSP a OUSA
🇸🇰Bratislava, Slovakia
Cancer Research UK Edinburgh Centre
🇬🇧Edinburgh, Edinburgh, CITY OF, United Kingdom
St Bartholomew's Hospital
🇬🇧London, London, CITY OF, United Kingdom
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
The Christie Hospital NHS Foundation Trust
🇬🇧Manchester, United Kingdom