A PHASE 1B/2, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07220060 IN COMBINATION WITH PF-07104091 PLUS ENDOCRINE THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
Overview
- Phase
- Phase 1
- Intervention
- PF-07220060 + PF-07104091 combination dose escalation
- Conditions
- Breast Cancer
- Sponsor
- Pfizer
- Enrollment
- 240
- Locations
- 49
- Primary Endpoint
- Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle
- Status
- Active, Not Recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •All Study Parts: Permanent treatment discontinuation from prior CDK 4 and/or CDK2 inhibitor due to treatment related toxicity.
- •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.
- •Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor for advanced disease.
- •Parts 2B and 2C: Prior treatment with an investigational endocrine therapy for advanced disease.
- •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.
- •Part 2C: Any prior systemic treatment for advanced disease.
- •Prior irradiation to \>25% of the bone marrow
- •Current use of drugs which have a risk for QTc prolongation
- •Current use or anticipated need for food or drugs that are known strong CYP3A4/5, strong UGT2B7 or UGT1A9 inhibitors or inducers
- •Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
Arms & Interventions
Part 1 Dose Escalation - Dose Level 1
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention: PF-07220060 + PF-07104091 combination dose escalation
Part 1 Dose Escalation - Dose Level 2
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention: PF-07220060 + PF-07104091 combination dose escalation
Part 1 Dose Escalation - Dose Level 3
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention: PF-07220060 + PF-07104091 combination dose escalation
Part 1 Dose Escalation - Dose Level 4
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention: PF-07220060 + PF-07104091 combination dose escalation
Part 1 Dose Escalation - Dose Level 5
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention: PF-07220060 + PF-07104091 combination dose escalation
Part 2A
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)
Intervention: PF-07104091 + PF-07220060 + fulvestrant dose expansion
Part 2B
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)
Intervention: PF-07104091 + PF-07220060 + fulvestrant dose expansion
Part 2C
PF-07220060 + PF-07104091 + Letrozole (ER+/HER2- Breast Cancer with no prior treatment with any CDK4/6 inhibitor for advanced disease)
Intervention: PF-07104091 + PF-07220060 + letrozole dose expansion
Part 1 Dose Escalation - Dose Level 6
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention: PF-07220060 + PF-07104091 combination dose escalation
Part 1 Dose Escalation - Dose Level 7
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention: PF-07220060 + PF-07104091 combination dose escalation
Part 1 Dose Escalation - Dose Level 8
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention: PF-07220060 + PF-07104091 combination dose escalation
Outcomes
Primary Outcomes
Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle
Time Frame: 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)
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
Time Frame: 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 Outcomes
- 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))
- 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))
- 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))
- 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))
- 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))