A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors
- Conditions
- Breast CancerSolid Tumors
- Interventions
- Drug: PF-07220060 + PF-07104091 combination dose escalation
- Registration Number
- NCT05262400
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 240
Not provided
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All Study Parts: Permanent treatment discontinuation from prior CDK 4 and/or CDK2 inhibitor due to treatment related toxicity.
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Part 2B and 1C: Prior treatment with any CDK 4/6 inhibitor, or SERDs (e.g. fulvestrant), or everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway for advanced disease.
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Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor for advanced disease.
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Parts 2B and 2C: Prior treatment with an investigational endocrine therapy for advanced disease.
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Part 2C: Prior neoadjuvant or adjuvant treatment with a nonsteroidal aromatase inhibitor AI (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.
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Part 2C: Any prior systemic treatment for advanced disease.
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Prior irradiation to >25% of the bone marrow
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Current use of drugs which have a risk for QTc prolongation
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Current use or anticipated need for food or drugs that are known strong CYP3A4/5, strong UGT2B7 or UGT1A9 inhibitors or inducers
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Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
- 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 of the cervix, Bowen's disease
- Major surgery within 4 weeks prior to study entry
- Radiation therapy within 4 weeks prior to study entry.
- Clinically important hypertension
- Known or suspected hypersensitivity to PF-07220060, PF-07104091, letrozole, fulvestrant, or goserelin (or equivalent to induce chemical menopause if applicable)
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Known abnormalities in coagulation. Anticoagulation with subcutaneous heparin or prophylactic doses of anticoagulant are allowed
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Known active uncontrolled or symptomatic central nervous system (CNS) metastases
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Active inflammatory GI disease
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Current use or anticipated need for Proton Pump Inhibitors (PPI) within 14 days prior to first dose of the study intervention
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Previous high-dose chemotherapy requiring stem cell rescue
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Participants with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
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Other protocol specific exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Dose Escalation - Dose Level 1 PF-07220060 + PF-07104091 combination dose escalation PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) Part 1 Dose Escalation - Dose Level 2 PF-07220060 + PF-07104091 combination dose escalation PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) Part 1 Dose Escalation - Dose Level 3 PF-07220060 + PF-07104091 combination dose escalation PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) Part 1 Dose Escalation - Dose Level 4 PF-07220060 + PF-07104091 combination dose escalation PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) Part 1 Dose Escalation - Dose Level 5 PF-07220060 + PF-07104091 combination dose escalation PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) Part 2C PF-07104091 + PF-07220060 + letrozole dose expansion PF-07220060 + PF-07104091 + Letrozole (ER+/HER2- Breast Cancer with no prior treatment with any CDK4/6 inhibitor for advanced disease) Part 1 Dose Escalation - Dose Level 6 PF-07220060 + PF-07104091 combination dose escalation PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) Part 1 Dose Escalation - Dose Level 7 PF-07220060 + PF-07104091 combination dose escalation PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) Part 1 Dose Escalation - Dose Level 8 PF-07220060 + PF-07104091 combination dose escalation PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) Part 2A PF-07104091 + PF-07220060 + fulvestrant dose expansion PF-07220060 + PF-07104091 + Fulvestrant (ER+/HER2- Breast Cancer with at least 1 prior systemic therapy for advanced or metastatic disease, including CDK4/6 inhibitor treatment and Endocrine Therapy) Part 2B PF-07104091 + PF-07220060 + fulvestrant dose expansion PF-07220060 + PF-07104091 + Fulvestrant (ER+/HER2- Breast Cancer with at least 1 prior endocrine therapy and up to 1 prior line of chemotherapy for advanced or metastatic disease and no prior treatment with any CDK4/6 inhibitor for advanced disease)
- Primary Outcome Measures
Name Time Method Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle Cycle 1 (28 days) Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level
Number of participants with treatment emergent adverse events (AEs) From baseline until end of study treatment or study completion (approximately 2 years) Incidence of participants with clinical laboratory abnormalities From baseline until end of study treatment or study completion (approximately 2 years) Number of participants with vital signs abnormalities From baseline until end of study treatment or study completion (approximately 2 years) Number of participants with corrected QT (QTc) interval From baseline until end of study treatment or study completion (approximately 2 years) 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
- Secondary Outcome Measures
Name Time Method Maximum plasma concentration (Cmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose 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 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 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 From baseline through disease progression or study completion (approximately 2 years) Percentage of participants with a best ORR of complete response (CR) or partial response (PR) using RECIST 1.
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 From baseline through time to event on study or study completion (approximately 2 years) Time from first assessment of event endpoint to last assessment of using RECIST 1.1
Duration of Response (DoR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole From baseline through time to event on study or study completion (approximately 2 years) 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
Progression-Free Survival (PFS) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole From baseline through time to event on study or study completion (approximately 2 years) 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 to Progression (TTP) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole From baseline through time to event on study or study completion (approximately 2 years) TTP is defined as the time from start date of treatment to the date of the first documentation of PD
Related Research Topics
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Trial Locations
- Locations (49)
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
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Scroll for more (39 remaining)Administrative Address: UCLA Hematology/Oncology🇺🇸Los Angeles, California, United States