Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors

Prostate Cancer Clinical Trial

— CDK4i  

Official title:

A PHASE 1/2A STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07220060 AS A SINGLE AGENT AND AS PART OF COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04557449
• Other study ID #: C4391001
• Secondary ID: 2020-002938-33
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 23, 2020
• Est. completion date: May 4, 2028

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2A, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060 administered as a single agent and then in combination with endocrine therapy.

Description:

The study consists of two parts and a China and Japan monotherapy cohort. Part 1 includes dose escalation cohorts evaluating PF-07220060 as single agent or in combination with endocrine therapy or enzalutamide, as well as a food effect cohort and a DDI cohort Part 2 includes dose expansion cohorts evaluating PF-07220060 in combination with endocrine therapy or enzalutamide.

In Part 1A, single escalating doses of PF-07220060 alone will be administered to determine the maximum tolerated dose (MTD) and select the recommended dose for expansion In Part 1B and Part 1C, PF-07220060 will be administered in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively).

In Part 1D, food effect assessment of PF-07220060 at the RP2D dose level from the Part 1A will be conducted In Part 1E, the effect of PF-07220060 on the PK of midazolam will be evaluated (DDI) In Part 1F, escalating dosed of PF-07220060 will be administered in combination with enzalutamide Part 1B and Part 1C may commence at MTD or before reaching the MTD at a dose level in Part 1A.

Part 2A is a dose expansion cohort with fulvestrant and will explore more than one dose of PF-07220060 in participants diagnosed with mBC.

Part 2B and Part 2C are expansion for combination therapy of PF-07220060 with letrozole and fulvestrant, respectively.

Part 2D is the expansion cohort for combination therapy of PF-07220060 with enzalutamide.

The China monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as single agent in Chinese participants.

The Japan monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as a single agent in Japanese participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 337
• Est. completion date: May 4, 2028
• Est. primary completion date: March 5, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Part 1: Breast Cancer (BC)

• Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) BC

• Part 1A/Part 1D/Part1E also include: Refractory HR-positive/HER2-positive BC

• Part 1: Tumors other than BC (Part 1A/Part 1D/Part 1E): NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests

• Part 1F: prostate cancer

• Part 2A, 2B and 2C:

• HR-positive/HER2-negative BC

• Patients who are either postmenopausal women or pre/peri-menopausal (Part 2C only)

• Part 1D: metastatic castration resistant prostate cancer

• Lesion:

• Part 1: evaluable lesion (including skin or bone lesion only)

• Part 2A, 2B and 2C: measurable lesion per RECIST v1.1

• Part 2D: Participants with evaluable disease as per PCWG3; participants with bone metastases only are allowed. Participants with biochemical recurrence only are excluded.

• Prior systemic Treatment

• Part 1: HR-positive/HER2-negative BC

• At least 1 line of SOC, including CD4/6 inhibitor therapy for advanced or metastatic disease, or if CDK4/6 inhibitors are not considered appropriate in the opinion of the investigator

• At least 1 line of anti-endocrine in countries without CDK4/6 inhibitor approval or reimbursement, for advanced or metastatic disease

• HR-positive/HER2-positive BC (Parts 1A/1D/1E): at least 1 prior treatment of approved HER2 targeting therapy

• Tumors other than BC (Parts 1A/1D/1E/1F): tumor that is resistant to at least 2 lines of SOC for advanced or recurrent disease or for which no standard therapy is available

• Part 2A: participants must have received at least 1 line of standard of care (including prior CDK4/6i) for advanced/metastatic disease; Prior chemo is allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed

• Part 2B: participants who have not received any prior systemic anti-cancer therapies for advanced/metastatic BC

• Part 2C:

• Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre or perimenopausal, or

• Progressed while on or within 1 month after the endo the prior aromatase inhibitor therapy for advanced/metastatic BC if postmenopausal or prior endocrine treatment for advanced/metastatic BC if pre or perimenopausal

• One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy

• Part 2D:

• Received prior abiraterone; enzalutamide and CDK4i naive

• 0-1 line of chemotherapy is allowed General Inclusion Criteria

• All participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1

• Adequate renal, liver, and bone marrow function

Exclusion Criteria:

• Part 1D: participants who have had a gastrectomy or have dietary or other restrictions that preclude a 10 hour overnight fast or consumption of the high fat, high calorie meal

• Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor

• Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway

• Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease

• Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ

• Major surgery or radiation within 4 weeks prior to study intervention

• Last anti-cancer treatment within 2 weeks prior to study intervention

• Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry

• Pregnant or breastfeeding female participant

• Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease

Related Conditions & MeSH terms

• Adenocarcinoma of Lung
• Breast Neoplasms
• CRC
• Liposarcoma
• Prostate Cancer
• Prostatic Neoplasms
• Solid Tumors

Intervention

Drug:
• PF-07220060
CDK4 inhibitor

Combination Product:
• Letrozole
Endocrine Therapy
• Fulvestrant
Endocrine Therapy

Drug:
• Midazolam
Benzodiazepine used for DDI

Combination Product:
• Enzalutamide
Androgen Receptor inhibitor

Locations

Country	Name	City	State
Argentina	Fundación Respirar	Buenos Aires
Argentina	Fundación Cenit Para La Investigación En Neurociencias	Caba	Ciudad Autã³noma DE Buenos Aires
Argentina	Hospital Británico de Buenos Aires	Ciudad autónoma de Buenos Aires	Buenos Aires
Argentina	Clínica Universitaria Reina Fabiola	Córdoba
Argentina	Fundación CORI para la Investigación y Prevención del Cáncer	La Rioja
China	Cancer Hospital Chinese Academy of Medical Science	Beijing	Beijing
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The first affiliated hospital of Ningbo University	Ningbo	Zhejiang
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Henan Cancer Hospital	Zhengzhou	Henan
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Mexico	INCAN	Cdmx	Distrito Federal
Mexico	Hospital MAC Periferico Sur	Ciudad de Mexico	Distrito Federal
Mexico	COI Centro Oncologico Internacional S.A.P.I. de C.V.	Mexico City	Distrito Federal
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEÓN
Mexico	Oaxaca Site Management Organization	Oaxaca
Mexico	Hospital Reforma	Oaxaca de Juárez	Oaxaca
Slovakia	Narodny onkologicky ustav	Bratislava
Slovakia	Onkologicky ustav sv. Alzbety, s.r.o., Interna klinika VSZaSP a OUSA	Bratislava
Slovakia	Fakultna nemocnica s poliklinikou Nove Zamky	Nove Zamky
Slovakia	POKO Poprad, s.r.o.	Poprad
United Kingdom	Cancer Research UK Edinburgh Centre	Edinburgh	Edinburgh, CITY OF
United Kingdom	Sarah Cannon Research Institute UK	London
United Kingdom	St Bartholomew's Hospital	London	London, CITY OF
United Kingdom	The Christie Hospital NHS Foundation Trust	Manchester
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Dana-Farber Cancer Institute (DFCI)	Boston	Massachusetts
United States	Tennessee Oncology, PLLC	Franklin	Tennessee
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Sarah Cannon Research Institute - Pharmacy	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Smilow Cancer Hospital at Yale - New Haven	New Haven	Connecticut
United States	Smilow Cancer Hospital Phase 1 Unit	New Haven	Connecticut
United States	Dana Farber Cancer Institute- Chestnut Hill	Newton	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  China,  Czechia,  Japan,  Mexico,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose limiting toxicities in the Dose Escalation Portion	First cycle (28 days) dose limiting toxicities (Parts 1A, 1B, 1C, 1F)	Baseline up to day 28 of Cycle 1.
Primary	Incidence of clinically significant AEs	Adverse Events	Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days
Primary	Incidence of clinically significant laboratory assessments	safety laboratory abnormalities	Weekly during Cycle 1 and 2 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months
Primary	Incidence of clinically significant abnormal vital and ECG parameters	vital signs and heart rate corrected QT interval	Day 1, Day 8, Day 15 of Cycle 1 and starting from Cycle 2, and then every 28 days through study completion, up to approximately 24 months (Each cycle is 28 days)
Primary	Food Effect	Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1D)	Day -7 through the end of Cycle 1
Primary	DDI	Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1E)	D1 to the end of Cycle 1
Secondary	Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point Within the Dose Interval (AUClast) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero Extrapolated to Infinity (AUCinf) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion	Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Tumor Response per RECIST v1.1 and per PCGW3	Per RECIST v1.1 (Part 1 A-E; Part 2B and 2C); per PCWG3 (Part 1F and Part 2D)	baseline up to approximately 24 months
Secondary	Duration of Response (DOR)	Per RECIST v1.1	baseline up to approximately 24 months
Secondary	Progression Free Survival (PFS)	PFS per RECIST v.1.1	baseline up to approximately 24 months
Secondary	Time to Progression (TTP)	TTP per RECIST v1.1	baseline up to approximately 24 months
Secondary	Clinical Benefit Rate (CBR)	CBR per RECIST v1.1 (Parts 2B, 2C)	baseline up to approximately 24 months
Secondary	Peak and Trough Concentration of PF-07220060	Peak and trough concentration (Parts 2B, 2C, 2D)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Peak and trough concentrations of enzalutamide and N-desmethyl enzalutamide	Peak and trough concentrations (Part 2D)	Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary	Time to first skeletal events	Time to first skeletal events (Part 2D)	Cycle 1 (each cycle is 28 days) to up to approximately 24 months
Secondary	Quality of life questionnaire	time to functional status deterioration by FACT-P (Part 2D)	Cycle 1 (each cycle is 28 days) to up to approximately 24 months
Secondary	Radiographic Progression Free survival	Part 2D	Cycle 1 (each cycle is 28 days) up to approximately 24 months
Secondary	PSA50	Part 1F and 2D	Cycle 1 (each cycle is 28 days) to up to approximately 24 months

External Links

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