A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors
Purpose
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.
Conditions
- Breast Cancer
- Solid Tumors
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Part 1: Breast Cancer (BC) - HR+, HER2- BC - Refractory HR-positive/HER2-positive BC - Part 1: Solid Tumors other than BC - Part 2: - HR-positive/HER2-negative BC - Lesion: - Part 1: evaluable lesion (including skin or bone lesion only) - Part 2: measurable lesion per RECIST v1.1 - Prior systemic Treatment - Part 1: HR-positive/HER2-negative BC - At least 1 line of SOC, including CDK4/6 inhibitor therapy and Endocrine Therapy, for advanced or metastatic disease. - Prior chemotherapy in the metastatic setting is allowed. - Part 1: HR-positive/HER2-positive BC - At least 1 prior treatment of approved HER2 targeting therapy. - Part 1: Solid Tumors other than BC - Participants with no standard therapy available or for which no local regulatory approved standard therapy is available that would confer significant clinical benefit in the medical judgement of the investigator. - Part 2A: At least 1 prior systemic therapy for advanced or metastatic disease, including CDK4/6 inhibitor treatment and ET. - Parts 2B: At least 1 prior endocrine therapy for advanced or metastatic disease. Progression during treatment or within 12 months of completion of adjuvant endocrine therapy is acceptable. - Part 2B: Up to 1 prior line of chemotherapy for advanced/metastatic disease is allowed. - General Inclusion Criteria - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 - Adequate renal, liver, and bone marrow function - Resolved acute effects of any prior therapy to baseline severity
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 - 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) - Known abnormalities in coagulation. Anticoagulation with subcutaneous heparin or prophylactic doses of anticoagulant are allowed - Known active uncontrolled or symptomatic central nervous system (CNS) metastases - Active inflammatory GI disease - Current use or anticipated need for Proton Pump Inhibitors (PPI) within 14 days prior to first dose of the study intervention - Previous high-dose chemotherapy requiring stem cell rescue - 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 - Other protocol specific exclusion criteria may apply
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1 Dose Escalation - Dose Level 1 |
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) |
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|
Experimental Part 1 Dose Escalation - Dose Level 2 |
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) |
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Experimental Part 1 Dose Escalation - Dose Level 3 |
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) |
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Experimental Part 1 Dose Escalation - Dose Level 4 |
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) |
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Experimental Part 1 Dose Escalation - Dose Level 5 |
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) |
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Experimental 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) |
|
|
Experimental 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) |
|
|
Experimental Part 2C |
PF-07220060 + PF-07104091 + Letrozole (ER+/HER2- Breast Cancer with no prior treatment with any CDK4/6 inhibitor for advanced disease) |
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|
Experimental Part 1 Dose Escalation - Dose Level 6 |
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) |
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Experimental Part 1 Dose Escalation - Dose Level 7 |
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) |
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Experimental Part 1 Dose Escalation - Dose Level 8 |
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors) |
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Recruiting Locations
Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Pfizer