Breast Cancer, Solid Tumors
Conditions
Keywords
cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), estrogen receptor-positive/human epidermal growth factor receptor 2 negative (ER+/HER2-), estrogen receptor-positive/refractory hormone receptor positive (ER+/HER2+), hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-)
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.
Interventions
DRUGPF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
DRUGPF-07104091 + PF-07220060 + fulvestrant dose expansion
PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
DRUGPF-07104091 + PF-07220060 + letrozole dose expansion
PF-07104091 and PF-07220060 will be administered orally in combination with letrozole
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Argentina, Brazil, Bulgaria, China, Czechia, Mexico, South Africa, Spain, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed