Study to Assess the Safety and Tolerability of PF-07220060 in Combination With PF-07104091 in Participants With Breast Cancers or Solid Tumors and to Assess the Safety and Tolerability of PF-07220060 and PF-07104091 in Combination With Endocrine Therapy in Participants With Breast Cancer.

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05262400

Collaborator

(none)

144

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To assess the safety and tolerability of increasing doses of PF-07220060 in combination with PF-07104091 and to estimate the Maximum Tolerated Dose (MTD) and/or select the Recommended dose for expansion (RDE) for PF-07220060 in combination with PF-07104091 in participants with breast cancers or solid tumors and to assess the safety and tolerability of the RDE of PF-07220060 and PF-07104091 in combination with Endocrine Therapy in participants with breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Solid Tumors	Drug: PF-07220060 + PF-07104091 combination dose escalation Drug: PF-07220060 + PF-07104091 combination dose escalation Drug: PF-07220060 + PF-07104091 combination dose escalation Drug: PF-07220060 + PF-07104091 combination dose escalation Drug: PF-07220060 + PF-07104091 combination dose escalation Drug: PF-07104091 + PF-07220060 + fulvestrant dose expansion Drug: PF-07104091 + PF-07220060 + fulvestrant dose expansion Drug: PF-07104091 + PF-07220060 + letrozole dose expansion	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 14, 2022

Anticipated Primary Completion Date :

Oct 12, 2026

Anticipated Study Completion Date :

Oct 12, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Dose Escalation - Dose Level 1 PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)	Drug: PF-07220060 + PF-07104091 combination dose escalation PF-07104091 and PF-07220060 will be administered orally
Experimental: Part 1 Dose Escalation - Dose Level 2 PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)	Drug: PF-07220060 + PF-07104091 combination dose escalation PF-07104091 and PF-07220060 will be administered orally
Experimental: Part 1 Dose Escalation - Dose Level 3 PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)	Drug: PF-07220060 + PF-07104091 combination dose escalation PF-07104091 and PF-07220060 will be administered orally
Experimental: Part 1 Dose Escalation - Dose Level 4 PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)	Drug: PF-07220060 + PF-07104091 combination dose escalation PF-07104091 and PF-07220060 will be administered orally
Experimental: Part 1 Dose Escalation - Dose Level 5 PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)	Drug: PF-07220060 + PF-07104091 combination dose escalation PF-07104091 and PF-07220060 will be administered orally
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)	Drug: PF-07104091 + PF-07220060 + fulvestrant dose expansion PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
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)	Drug: PF-07104091 + PF-07220060 + fulvestrant dose expansion PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
Experimental: Part 2C PF-07220060 + PF-07104091 + Letrozole (ER+/HER2- Breast Cancer with no prior treatment with any CDK4/6 inhibitor for advanced disease)	Drug: PF-07104091 + PF-07220060 + letrozole dose expansion PF-07104091 and PF-07220060 will be administered orally in combination with letrozole

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 2A and 2B: At least 1 prior endocrine therapy for advanced or metastatic disease.
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: Prior treatment with any CDK 4/6 inhibitor, or fulvestrant, or everolimus.
Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor 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.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	START Midwest	Grand Rapids	Michigan	United States	49546
3	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030