The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Clinical Trial Details
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Breast Cancer
CDK2 Inhibitor
PF-07104091 is an investigational compound. Its safety and efficacy have not been established.
CDK4 Inhibitor
PF-07220060 is an investigational compound. Its safety and efficacy have not been established.
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
Phase 1 /2
NCT05262400
Active enrolling
Locations
United States, Argentina, Brazil, Bulgaria, China, Czechia, Mexico, South Africa, Spain
Study design
Participant Group/Arm
EXPERIMENTAL: Part 1 Dose Escalation - Dose Level 1
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention/Treatment
DRUG: PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
Participant Group/Arm
EXPERIMENTAL: Part 1 Dose Escalation - Dose Level 2
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention/Treatment
DRUG: PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
Participant Group/Arm
EXPERIMENTAL: Part 1 Dose Escalation - Dose Level 3
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention/Treatment
DRUG: PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
Participant Group/Arm
EXPERIMENTAL: Part 1 Dose Escalation - Dose Level 4
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention/Treatment
DRUG: PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
Participant Group/Arm
EXPERIMENTAL: Part 1 Dose Escalation - Dose Level 5
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention/Treatment
DRUG: PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
Participant Group/Arm
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)
Intervention/Treatment
DRUG: PF-07104091 + PF-07220060 + fulvestrant dose expansion
PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
Participant Group/Arm
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)
Intervention/Treatment
DRUG: PF-07104091 + PF-07220060 + fulvestrant dose expansion
PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
Participant Group/Arm
EXPERIMENTAL: Part 2C
PF-07220060 + PF-07104091 + Letrozole (ER+/HER2- Breast Cancer with no prior treatment with any CDK4/6 inhibitor for advanced disease)
Intervention/Treatment
DRUG: PF-07104091 + PF-07220060 + letrozole dose expansion
PF-07104091 and PF-07220060 will be administered orally in combination with letrozole
Participant Group/Arm
EXPERIMENTAL: Part 1 Dose Escalation - Dose Level 6
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention/Treatment
DRUG: PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
Participant Group/Arm
EXPERIMENTAL: Part 1 Dose Escalation - Dose Level 7
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention/Treatment
DRUG: PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
Participant Group/Arm
EXPERIMENTAL: Part 1 Dose Escalation - Dose Level 8
PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Intervention/Treatment
DRUG: PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
Key eligibility criteria
Inclusion criteria
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 applicabl
- 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
Key dates
Study start date
- March 2022
Estimated primary completion date
- December 2026
Key endpoints
Primary Outcome Measures
Outcome Measure
Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle
Measure Description
Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level
Time Frame
Cycle 1 (28 days)
Outcome Measure
Number of participants with treatment emergent adverse events (AEs)
Time Frame
From baseline until end of study treatment or study completion (approximately 2 years)
Outcome Measure
Incidence of participants with clinical laboratory abnormalities
Time Frame
From baseline until end of study treatment or study completion (approximately 2 years)
Outcome Measure
Number of participants with vital signs abnormalities
Time Frame
From baseline until end of study treatment or study completion (approximately 2 years)
Outcome Measure
Number of participants with corrected QT (QTc) interval
Measure Description
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
Time Frame
From baseline until end of study treatment or study completion (approximately 2 years)
Secondary Outcome Measures:
Outcome Measure
Maximum plasma concentration (Cmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose
Time Frame
Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Outcome Measure
Time to maximum plasma concentration (Tmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose
Time Frame
Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Outcome Measure
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
Time Frame
Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Outcome Measure
Objective response rate (ORR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
Measure Description
Percentage of participants with a best ORR of complete response (CR) or partial response (PR) using RECIST 1.
Time Frame
From baseline through disease progression or study completion (approximately 2 years)
Outcome Measure
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
Measure Description
Time from first assessment of event endpoint to last assessment of using RECIST 1.1
Time Frame
From baseline through time to event on study or study completion (approximately 2 years)
Outcome Measure
Duration of Response (DoR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
Measure Description
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
Time Frame
From baseline through time to event on study or study completion (approximately 2 years)
Outcome Measure
Progression-Free Survival (PFS) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
Measure Description
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 Frame
From baseline through time to event on study or study completion (approximately 2 years)
Outcome Measure
Time to Progression (TTP) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
Measure Description
TTP is defined as the time from start date of treatment to the date of the first documentation of PD
Time Frame
From baseline through time to event on study or study completion (approximately 2 years)
Number of participants
240
Collaborators and investigators
Sponsor: Pfizer
Collaborator: None