Clinical trial NCT05262400: A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Solid Tumors
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-)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-03-02
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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 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

Primary outcomes:
measure: Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle
timeFrame: Cycle 1 (28 days)
measure: Number of participants with treatment emergent adverse events (AEs)
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
measure: Incidence of participants with clinical laboratory abnormalities
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
measure: Number of participants with vital signs abnormalities
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
measure: Number of participants with corrected QT (QTc) interval
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: Time to maximum plasma concentration (Tmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
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
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: Objective response rate (ORR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
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
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
measure: Duration of Response (DoR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
measure: Progression-Free Survival (PFS) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
measure: Time to Progression (TTP) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Administrative Address: UCLA Hematology/Oncology
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology / Oncology-Parkside
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology-Santa Monica
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Viedma
country: Argentina
facility: Clinica Viedma S. A
state: RÍO Negro
city: Buenos Aires
country: Argentina
facility: Centro Oncologico Korben
city: Córdoba
country: Argentina
facility: Clínica Universitaria Reina Fabiola
city: La Rioja
country: Argentina
facility: Fundación CORI para la Investigación y Prevención del Cáncer
city: Ijui
country: Brazil
facility: ONCOSITE - Centro de Pesquisa Clinica em Oncologia
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisa Clínica - Área Administrativa
state: RIO Grande DO SUL
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos
state: SÃO Paulo
city: São Paulo
country: Brazil
facility: Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Serdika EOOD
state: Sofia (stolitsa)
city: Haskovo
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology - Haskovo
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center - Plovdiv EOOD
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Serdika EOOD
city: Vratsa
country: Bulgaria
facility: Complex Oncology Center - Vratsa
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
state: Olomoucký KRAJ
city: Prague
country: Czechia
facility: Fakultni nemocnice Bulovka
state: Praha 8
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo LEÓN
city: Merida
country: Mexico
facility: Mérida Investigación Clínica
state: Yucatán
city: Bloemfontein
country: South Africa
facility: FARMOVS
state: FREE State
city: Johannesburg
country: South Africa
facility: 15 Eton Road
state: Gauteng
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Johannesburg
country: South Africa
facility: WCR Office
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Clinical Research
state: Gauteng
city: Pretoria
country: South Africa
facility: Wilgers Oncology Centre
state: Gauteng
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario
state: A Coruña [LA Coruña]
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalunya [cataluña]
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid, Comunidad DE
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
state: Madrid, Comunidad DE
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: