Clinical trial NCT04557449: Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Liposarcoma
Prostate Cancer
Breast Neoplasms
Adenocarcinoma of Lung
Keywords: CDK4 inhibitor
Breast cancer
enzalutamide
fulvestrant
letrozole
endocrine therapy
Colorectal Cancer (CRC)
Solid Tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-09-21
Enrollment: 337
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: 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.

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.

Part 2E is an expansion cohort to evaluate PF-07220060 Monotherapy versus PF-07220060 plus fulvestrant combination therapy. 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.


Eligibility criteria: 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, 2C and 2E:

  * 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, 2C and 2E: 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 and 2E: 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

Primary outcomes:
measure: Number of participants with dose limiting toxicities in the Dose Escalation Portion
timeFrame: Baseline up to day 28 of Cycle 1.
measure: Incidence of clinically significant AEs
timeFrame: Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days
measure: Incidence of clinically significant laboratory assessments
timeFrame: Weekly during Cycle 1 and 2 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months
measure: Incidence of clinically significant abnormal vital and ECG parameters
timeFrame: 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)
measure: Food Effect
timeFrame: Day -7 through the end of Cycle 1
measure: DDI
timeFrame: D1 to the end of Cycle 1
Secondary outcomes:
measure: Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: 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
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: 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
timeFrame: 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
measure: Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Tumor Response per RECIST v1.1 and per PCGW3
timeFrame: baseline up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: baseline up to approximately 24 months
measure: Progression Free Survival (PFS)
timeFrame: baseline up to approximately 24 months
measure: Time to Progression (TTP)
timeFrame: baseline up to approximately 24 months
measure: Clinical Benefit Rate (CBR)
timeFrame: baseline up to approximately 24 months
measure: Peak and Trough Concentration of PF-07220060
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Peak and trough concentrations of enzalutamide and N-desmethyl enzalutamide
timeFrame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
measure: Time to first skeletal events
timeFrame: Cycle 1 (each cycle is 28 days) to up to approximately 24 months
measure: Quality of life questionnaire
timeFrame: Cycle 1 (each cycle is 28 days) to up to approximately 24 months
measure: Radiographic Progression Free survival
timeFrame: Cycle 1 (each cycle is 28 days) up to approximately 24 months
measure: PSA50
timeFrame: Cycle 1 (each cycle is 28 days) to up to approximately 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ellison Institute
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale - New Haven
state: Connecticut
city: New Haven
country: United States
facility: Yale-New Haven Hospital-Yale Cancer Center
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital Phase 1 Unit
state: Connecticut
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Newton
country: United States
facility: Dana Farber Cancer Institute- Chestnut Hill
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Pharmacy
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Ciudad autónoma de Buenos Aires
country: Argentina
facility: Hospital Británico de Buenos Aires
state: Buenos Aires
city: Caba
country: Argentina
facility: Fundación Cenit Para La Investigación En Neurociencias
state: Ciudad Autã³noma DE Buenos Aires
city: Buenos Aires
country: Argentina
facility: Fundación Respirar
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: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Cdmx
country: Mexico
facility: INCAN
state: Distrito Federal
city: Ciudad de Mexico
country: Mexico
facility: Hospital MAC Periferico Sur
state: Distrito Federal
city: Mexico City
country: Mexico
facility: COI Centro Oncologico Internacional S.A.P.I. de C.V.
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo LEÓN
city: Oaxaca de Juárez
country: Mexico
facility: Hospital Reforma
state: Oaxaca
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization
city: Bratislava
country: Slovakia
facility: Onkologicky ustav sv. Alzbety, s.r.o., Interna klinika VSZaSP a OUSA
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Nove Zamky
country: Slovakia
facility: Fakultna nemocnica s poliklinikou Nove Zamky
city: Poprad
country: Slovakia
facility: POKO Poprad, s.r.o.
city: Edinburgh
country: United Kingdom
facility: Cancer Research UK Edinburgh Centre
state: Edinburgh, CITY OF
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
state: London, CITY OF
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Manchester
country: United Kingdom
facility: The Christie Hospital NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: