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Active, not recruitingNCT04557449CDK4iUpdated Aug 20, 2026

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

A Phase 2 interventional study of PF-07220060 and Letrozole in Liposarcoma, Prostate Cancer and Breast Neoplasms, sponsored by Pfizer. Active, not recruiting at 39 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-20.

Sponsored by Pfizer · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
362
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Liposarcoma
  • Prostate Cancer
  • Breast Neoplasms
  • Adenocarcinoma of Lung

Keywords

  • CDK4 inhibitor
  • Breast cancer
  • enzalutamide
  • fulvestrant
  • letrozole
  • endocrine therapy
  • Colorectal Cancer (CRC)
  • Solid Tumors
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
362 participants (actual)

Study arms

  • Experimental
    1A Monotherapy Escalation Arm 1

    PF-07220060 Monotherapy Escalation

    Drug: PF-07220060

  • Experimental
    1A Monotherapy Escalation Arm 2

    PF-07220060 Monotherapy Escalation

    Drug: PF-07220060

  • Experimental
    1A Monotherapy Escalation Arm 3

    PF-07220060 Monotherapy Escalation

    Drug: PF-07220060

  • Experimental
    1A Monotherapy Escalation Arm 4

    PF-07220060 Monotherapy Escalation

    Drug: PF-07220060

  • Experimental
    1B Combination Dose Finding Arm 1

    PF-07220060 with Letrozole combination Escalation

    Drug: PF-07220060 · Combination Product: Letrozole

  • Experimental
    1B Combination Dose Finding Arm 2

    PF-07220060 with Letrozole Combination Escalation

    Drug: PF-07220060 · Combination Product: Letrozole

  • Experimental
    1C Combination Dose Finding Arm 1

    PF-07220060 with Fulvestrant Combination Escalation

    Drug: PF-07220060 · Combination Product: Fulvestrant

  • Experimental
    1C Combination Dose Finding Arm 2

    PF-07220060 with Fulvestrant Combination Escalation

    Drug: PF-07220060 · Combination Product: Fulvestrant

  • Experimental
    2B Combination Dose Expansion

    PF-07220060 with Letrozole Combination Expansion

    Drug: PF-07220060 · Combination Product: Letrozole

  • Experimental
    2C Combination Dose Expansion

    PF-07220060 with fulvestrant Combination Expansion

    Drug: PF-07220060 · Combination Product: Fulvestrant

  • Experimental
    1D Monotherapy Food Effect

    PF-07220060 Monotherapy Food Effect

    Drug: PF-07220060

  • Experimental
    1A Monotherapy Escalation Arm 5

    PF-07220060 Monotherapy Escalation

    Drug: PF-07220060

  • Experimental
    1F Combination Dose Finding

    PF-07220060 with Enzalutamide Escalation

    Drug: PF-07220060 · Combination Product: Enzalutamide

  • Experimental
    1E DDI Cohort

    PF-07220060 DDI with Midazolam

    Drug: PF-07220060 · Drug: Midazolam

  • Experimental
    2D Combination Dose Expansion

    PF-07220060 with enzalutamide Combination Expansion

    Drug: PF-07220060 · Combination Product: Enzalutamide

  • Experimental
    2A Combination Dose Expansion

    PF-07220060 with fulvestrant combination dose expansion

    Drug: PF-07220060 · Combination Product: Fulvestrant

  • Experimental
    2E Combination Dose Expansion

    PF-07220060 Monotherapy OR PF-07220060 plus fulvestrant combination therapy

    Drug: PF-07220060 · Combination Product: Fulvestrant

Interventions

  • DrugPF-07220060

    CDK4 inhibitor

  • Combination productLetrozole

    Endocrine Therapy

    Also known as: Femara

  • Combination productFulvestrant

    Endocrine Therapy

    Also known as: Faslodex

  • DrugMidazolam

    Benzodiazepine used for DDI

  • Combination productEnzalutamide

    Androgen Receptor inhibitor

    Also known as: Xtandi

05

What researchers measure

Primary outcomes

  1. Number of participants with dose limiting toxicities in the Dose Escalation Portion

    First cycle (28 days) dose limiting toxicities (Parts 1A, 1B, 1C, 1F)

    Time frame: Baseline up to day 28 of Cycle 1.

  2. Incidence of clinically significant AEs

    Adverse Events

    Time frame: Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days

  3. Incidence of clinically significant laboratory assessments

    safety laboratory abnormalities

    Time frame: Weekly during Cycle 1 and 2 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months

  4. Incidence of clinically significant abnormal vital and ECG parameters

    vital signs and heart rate corrected QT interval

    Time frame: 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)

  5. Food Effect

    Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1D)

    Time frame: Day -7 through the end of Cycle 1

  6. DDI

    Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1E)

    Time frame: D1 to the end of Cycle 1

Secondary outcomes

  1. Single Dose: Maximal concentration (Cmax) 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

  2. 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)

    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

  3. 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)

    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

  4. 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: 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

  5. Apparent Oral Plasma Clearance (CL/F) 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

  6. 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)

    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

  7. 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)

    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

  8. 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)

    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

  9. 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)

    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

  10. 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)

    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

  11. 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)

    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

  12. 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)

    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

  13. 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)

    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

  14. 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)

    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

  15. 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)

    Time frame: baseline up to approximately 24 months

  16. Duration of Response (DOR)

    Per RECIST v1.1

    Time frame: baseline up to approximately 24 months

  17. Progression Free Survival (PFS)

    PFS per RECIST v.1.1

    Time frame: baseline up to approximately 24 months

  18. Time to Progression (TTP)

    TTP per RECIST v1.1

    Time frame: baseline up to approximately 24 months

  19. Clinical Benefit Rate (CBR)

    CBR per RECIST v1.1 (Parts 2B, 2C)

    Time frame: baseline up to approximately 24 months

  20. Peak and Trough Concentration of PF-07220060

    Peak and trough concentration (Parts 2B, 2C, 2D)

    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

  21. Peak and trough concentrations of enzalutamide and N-desmethyl enzalutamide

    Peak and trough concentrations (Part 2D)

    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

  22. Time to first skeletal events

    Time to first skeletal events (Part 2D)

    Time frame: Cycle 1 (each cycle is 28 days) to up to approximately 24 months

  23. Quality of life questionnaire

    time to functional status deterioration by FACT-P (Part 2D)

    Time frame: Cycle 1 (each cycle is 28 days) to up to approximately 24 months

  24. Radiographic Progression Free survival

    Part 2D

    Time frame: Cycle 1 (each cycle is 28 days) up to approximately 24 months

  25. PSA50

    Part 1F and 2D

    Time frame: Cycle 1 (each cycle is 28 days) to up to approximately 24 months

06

Study locations

39 sites
  • Ellison Institute
    Los Angeles, California 90064, United States
  • Smilow Cancer Hospital - Yale New Haven Health
    New Haven, Connecticut 06510, United States
  • Yale-New Haven Hospital-Yale Cancer Center
    New Haven, Connecticut 06510, United States
  • Smilow Cancer Hospital Phase 1 Unit
    New Haven, Connecticut 06511, United States
  • Yale University - Smilow Cancer Hospital; C/O Thomas Ferencz, RPh, BCOP
    New Haven, Connecticut 06511, United States
  • Smilow Cancer Hospital - Trumbull
    Trumbull, Connecticut 06611, United States
  • Brigham & Women's Hospital
    Boston, Massachusetts 02115, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Dana Farber Cancer Institute- Chestnut Hill
    Newton, Massachusetts 02467, United States
  • START Midwest
    Grand Rapids, Michigan 49546, United States
  • Sarah Cannon Research Institute - Pharmacy
    Nashville, Tennessee 37203, United States
  • SCRI Oncology Partners
    Nashville, Tennessee 37203, United States
  • The University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • The University of Texas, MD Anderson Cancer Center - West Houston
    Houston, Texas 77079, United States
  • Hospital Británico de Buenos Aires
    Ciudad Autónoma de Buenos Aires, Buenos Aires 1280, Argentina
  • Fundación Cenit Para La Investigación En Neurociencias
    CABA, Ciudad Autã³noma de Buenos Aires 1125, Argentina
  • Fundación Respirar
    Buenos Aires, C1426ABP, Argentina
  • Clínica Universitaria Reina Fabiola
    Córdoba, X50004FHP, Argentina
  • Fundación CORI para la Investigación y Prevención del Cáncer
    La Rioja, F5300COE, Argentina
  • Cancer Hospital Chinese Academy of Medical Science
    Beijing, Beijing Municipality 100021, China
  • Henan Cancer Hospital
    Zhengzhou, Henan 450008, China
  • Hubei Cancer Hospital
    Wuhan, Hubei 430079, China
  • The First Affiliated Hospital of Xi'an Jiaotong University
    Xi’an, Shanxi 710061, China
  • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    Hangzhou, Zhejiang 310016, China
  • Vseobecna fakultni nemocnice v Praze
    Prague, 12808, Czechia
  • National Cancer Center Hospital East
    Kashiwa, Chiba 277-8577, Japan
  • COI Centro Oncologico Internacional S.A.P.I. de C.V.
    Mexico City, Mexico City 04700, Mexico
  • Hospital MAC Periferico Sur
    Mexico City, Mexico City 04700, Mexico
  • INCAN
    Mexico City, Mexico City 14080, Mexico
  • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
    Monterrey, Nuevo León 64460, Mexico
  • Hospital Reforma
    Oaxaca City, Oaxaca 68000, Mexico
  • Oaxaca Site Management Organization
    Oaxaca City, 68000, Mexico
  • Onkologicky ustav sv. Alzbety, s.r.o., Interna klinika VSZaSP a OUSA
    Bratislava, 812 50, Slovakia
  • Narodny onkologicky ustav
    Bratislava, 833 10, Slovakia
  • Fakultna nemocnica s poliklinikou Nove Zamky
    Nové Zámky, 940 34, Slovakia
  • Cancer Research UK Edinburgh Centre
    Edinburgh, Edinburgh, CITY of EH4 2XR, United Kingdom
  • St Bartholomew's Hospital
    London, London, CITY of EC1A 7BE, United Kingdom
  • Sarah Cannon Research Institute UK
    London, W1G 6AD, United Kingdom
  • The Christie Hospital NHS Foundation Trust
    Manchester, M20 4BX, United Kingdom
07

References and documents

Individual participant data

Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

08

Registry details

Key details

Study ID
NCT04557449
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Sep 21, 2020
Start date
Sep 23, 2020
Primary completion
Sep 23, 2026 (estimated)
Completion
Nov 23, 2027 (estimated)
Last update
Aug 20, 2026

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
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