A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors

Phase 1

Active, not recruiting

• Conditions: Breast Cancer; Solid Tumors
• Interventions: Drug: PF-07220060 + PF-07104091 combination dose escalation; Drug: PF-07104091 + PF-07220060 + letrozole dose expansion; Drug: PF-07104091 + PF-07220060 + fulvestrant dose expansion

• Registration Number: NCT05262400
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-02-21
• Study First Submitted QC: 2022-02-21
• Study First Posted: 2022-03-02
• Study Start: 2022-03-14
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-18
• Primary Completion: 2026-08-23
• Study Completion: 2026-08-23

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Not provided

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 Dose Escalation - Dose Level 1	PF-07220060 + PF-07104091 combination dose escalation	PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Part 1 Dose Escalation - Dose Level 2	PF-07220060 + PF-07104091 combination dose escalation	PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Part 1 Dose Escalation - Dose Level 3	PF-07220060 + PF-07104091 combination dose escalation	PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Part 1 Dose Escalation - Dose Level 4	PF-07220060 + PF-07104091 combination dose escalation	PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Part 1 Dose Escalation - Dose Level 5	PF-07220060 + PF-07104091 combination dose escalation	PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Part 2C	PF-07104091 + PF-07220060 + letrozole dose expansion	PF-07220060 + PF-07104091 + Letrozole (ER+/HER2- Breast Cancer with no prior treatment with any CDK4/6 inhibitor for advanced disease)
Part 1 Dose Escalation - Dose Level 6	PF-07220060 + PF-07104091 combination dose escalation	PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Part 1 Dose Escalation - Dose Level 7	PF-07220060 + PF-07104091 combination dose escalation	PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Part 1 Dose Escalation - Dose Level 8	PF-07220060 + PF-07104091 combination dose escalation	PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)
Part 2A	PF-07104091 + PF-07220060 + fulvestrant dose expansion	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)
Part 2B	PF-07104091 + PF-07220060 + fulvestrant dose expansion	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)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (49)

Administrative Address: UCLA Hematology/Oncology; 🇺🇸 Los Angeles, California, United States

Ronald Reagan UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

UCLA Hematology/Oncology; 🇺🇸 Los Angeles, California, United States

UCLA Hematology / Oncology-Parkside; 🇺🇸 Santa Monica, California, United States

UCLA Hematology/Oncology-Santa Monica; 🇺🇸 Santa Monica, California, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Saint Luke's Cancer Institute; 🇺🇸 Kansas City, Missouri, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Swedish Medical Center; 🇺🇸 Seattle, Washington, United States

Clinica Viedma S. A; 🇦🇷 Viedma, RÍO Negro, Argentina

Centro Oncologico Korben; 🇦🇷 Buenos Aires, Argentina

Clínica Universitaria Reina Fabiola; 🇦🇷 Córdoba, Argentina

Fundación CORI para la Investigación y Prevención del Cáncer; 🇦🇷 La Rioja, Argentina

ONCOSITE - Centro de Pesquisa Clinica em Oncologia; 🇧🇷 Ijui, RIO Grande DO SUL, Brazil

Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Centro de Pesquisa Clínica - Área Administrativa; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Fundação Pio XII - Hospital de Câncer de Barretos; 🇧🇷 Barretos, SÃO Paulo, Brazil

Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda; 🇧🇷 São Paulo, Brazil

Multiprofile Hospital for Active Treatment Serdika EOOD; 🇧🇬 Sofia, Bulgaria

Specialized Hospital for Active Treatment of Oncology - Haskovo; 🇧🇬 Haskovo, Bulgaria

Complex Oncology Center - Plovdiv EOOD; 🇧🇬 Plovdiv, Bulgaria

Complex Oncology Center - Vratsa; 🇧🇬 Vratsa, Bulgaria

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

West China Hospital of Sichuan University; 🇨🇳 Chengdu, Sichuan, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Tianjin Medical University Cancer Institute & Hospital; 🇨🇳 Tianjin, Tianjin, China

Sir Run Run Shaw Hospital of Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

Sir Run Run Shaw Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Fakultni nemocnice Olomouc; 🇨🇿 Olomouc, Olomoucký KRAJ, Czechia

Fakultni nemocnice Bulovka; 🇨🇿 Prague, Praha 8, Czechia

Vseobecna fakultni nemocnice v Praze; 🇨🇿 Praha 2, Czechia

Instituto Nacional de Cancerologia; 🇲🇽 Mexico City, Distrito Federal, Mexico

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"; 🇲🇽 Monterrey, Nuevo LEÓN, Mexico

Mérida Investigación Clínica; 🇲🇽 Merida, Yucatán, Mexico

FARMOVS; 🇿🇦 Bloemfontein, FREE State, South Africa

15 Eton Road; 🇿🇦 Johannesburg, Gauteng, South Africa

Charlotte Maxeke Johannesburg Academic Hospital; 🇿🇦 Johannesburg, Gauteng, South Africa

WCR Office; 🇿🇦 Johannesburg, Gauteng, South Africa

Wits Clinical Research; 🇿🇦 Johannesburg, Gauteng, South Africa

Wilgers Oncology Centre; 🇿🇦 Pretoria, Gauteng, South Africa

CHUS - Hospital Clinico Universitario; 🇪🇸 Santiago de Compostela, A Coruña [LA Coruña], Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Barcelona [barcelona], Spain

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Catalunya [cataluña], Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Madrid, Comunidad DE, Spain

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Madrid, Comunidad DE, Spain

Hospital Universitario Virgen Del Rocio; 🇪🇸 Sevilla, Spain