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

NCT04557449 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: C43910012024-512120-11-00
• Study Type: interventional
• Target: 362
• Locations: 8 countries
• Sites: 38

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.

Conditions

Liposarcoma; Prostate Cancer; Breast Neoplasms; Adenocarcinoma of Lung

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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.

• 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

• 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

• 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)

• Food Effect

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

  Day -7 through the end of Cycle 1

• DDI

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

  D1 to the end of Cycle 1

Secondary Outcomes (25)

• Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion

  Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months

• Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion

  Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months

• 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

  Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months

• 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

  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

• Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion

  Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months

Study Arms (17)

1A Monotherapy Escalation Arm 1

EXPERIMENTAL

PF-07220060 Monotherapy Escalation

Drug: PF-07220060

1A Monotherapy Escalation Arm 2

EXPERIMENTAL

PF-07220060 Monotherapy Escalation

Drug: PF-07220060

1A Monotherapy Escalation Arm 3

EXPERIMENTAL

PF-07220060 Monotherapy Escalation

Drug: PF-07220060

1A Monotherapy Escalation Arm 4

EXPERIMENTAL

PF-07220060 Monotherapy Escalation

Drug: PF-07220060

1B Combination Dose Finding Arm 1

EXPERIMENTAL

PF-07220060 with Letrozole combination Escalation

Drug: PF-07220060; Combination Product: Letrozole

1B Combination Dose Finding Arm 2

EXPERIMENTAL

PF-07220060 with Letrozole Combination Escalation

Drug: PF-07220060; Combination Product: Letrozole

1C Combination Dose Finding Arm 1

EXPERIMENTAL

PF-07220060 with Fulvestrant Combination Escalation

Drug: PF-07220060; Combination Product: Fulvestrant

1C Combination Dose Finding Arm 2

EXPERIMENTAL

PF-07220060 with Fulvestrant Combination Escalation

Drug: PF-07220060; Combination Product: Fulvestrant

2B Combination Dose Expansion

EXPERIMENTAL

PF-07220060 with Letrozole Combination Expansion

Drug: PF-07220060; Combination Product: Letrozole

2C Combination Dose Expansion

EXPERIMENTAL

PF-07220060 with fulvestrant Combination Expansion

Drug: PF-07220060; Combination Product: Fulvestrant

1D Monotherapy Food Effect

EXPERIMENTAL

PF-07220060 Monotherapy Food Effect

Drug: PF-07220060

1A Monotherapy Escalation Arm 5

EXPERIMENTAL

PF-07220060 Monotherapy Escalation

Drug: PF-07220060

1F Combination Dose Finding

EXPERIMENTAL

PF-07220060 with Enzalutamide Escalation

Drug: PF-07220060; Combination Product: Enzalutamide

1E DDI Cohort

EXPERIMENTAL

PF-07220060 DDI with Midazolam

Drug: PF-07220060; Drug: Midazolam

2D Combination Dose Expansion

EXPERIMENTAL

PF-07220060 with enzalutamide Combination Expansion

Drug: PF-07220060; Combination Product: Enzalutamide

2A Combination Dose Expansion

EXPERIMENTAL

PF-07220060 with fulvestrant combination dose expansion

Drug: PF-07220060; Combination Product: Fulvestrant

2E Combination Dose Expansion

EXPERIMENTAL

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

Drug: PF-07220060; Combination Product: Fulvestrant

Interventions

PF-07220060 DRUG

CDK4 inhibitor

1A Monotherapy Escalation Arm 1; 1A Monotherapy Escalation Arm 2; 1A Monotherapy Escalation Arm 3; 1A Monotherapy Escalation Arm 4; 1A Monotherapy Escalation Arm 5; 1B Combination Dose Finding Arm 1; 1B Combination Dose Finding Arm 2; 1C Combination Dose Finding Arm 1; 1C Combination Dose Finding Arm 2; 1D Monotherapy Food Effect; 1E DDI Cohort; 1F Combination Dose Finding; 2A Combination Dose Expansion; 2B Combination Dose Expansion; 2C Combination Dose Expansion; 2D Combination Dose Expansion; 2E Combination Dose Expansion

Letrozole COMBINATION_PRODUCT

Endocrine Therapy

Also known as: Femara

1B Combination Dose Finding Arm 1; 1B Combination Dose Finding Arm 2; 2B Combination Dose Expansion

Fulvestrant COMBINATION_PRODUCT

Endocrine Therapy

Also known as: Faslodex

1C Combination Dose Finding Arm 1; 1C Combination Dose Finding Arm 2; 2A Combination Dose Expansion; 2C Combination Dose Expansion; 2E Combination Dose Expansion

Midazolam DRUG

Benzodiazepine used for DDI

1E DDI Cohort

Enzalutamide COMBINATION_PRODUCT

Androgen Receptor inhibitor

Also known as: Xtandi

1F Combination Dose Finding; 2D Combination Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (38)

Ellison Institute

Los Angeles, California, 90064, United States

Location

Smilow Cancer Hospital at Yale - New Haven

New Haven, Connecticut, 06510, United States

Location

Yale-New Haven Hospital-Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, 06511, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute- Chestnut Hill

Newton, Massachusetts, 02459, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee, 37203, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Hospital Británico de Buenos Aires

Ciudad Autónoma de Buenos Aires, Buenos Aires, 1280, Argentina

Location

Fundación Cenit Para La Investigación En Neurociencias

CABA, Ciudad Autã³noma de Buenos Aires, 1125, Argentina

Location

Fundación Respirar

Buenos Aires, C1426ABP, Argentina

Location

Clínica Universitaria Reina Fabiola

Córdoba, X50004FHP, Argentina

Location

Fundación CORI para la Investigación y Prevención del Cáncer

La Rioja, F5300COE, Argentina

Location

Cancer Hospital Chinese Academy of Medical Science

Beijing, Beijing Municipality, 100021, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, 710061, China

Location

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

Fakultni nemocnice Olomouc

Olomouc, 779 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 12808, Czechia

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Hospital MAC Periferico Sur

Mexico City, Mexico City, 04700, Mexico

Location

INCAN

Mexico City, Mexico City, 14080, Mexico

Location

COI Centro Oncologico Internacional S.A.P.I. de C.V.

Mexico City, Mexico City, Mexico

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, 64460, Mexico

Location

Hospital Reforma

Oaxaca City, Oaxaca, 68000, Mexico

Location

Oaxaca Site Management Organization

Oaxaca City, 68000, Mexico

Location

Onkologicky ustav sv. Alzbety, s.r.o., Interna klinika VSZaSP a OUSA

Bratislava, 812 50, Slovakia

Location

Narodny onkologicky ustav

Bratislava, 833 10, Slovakia

Location

Fakultna nemocnica s poliklinikou Nove Zamky

Nové Zámky, 940 34, Slovakia

Location

POKO Poprad, s.r.o.

Poprad, 058 01, Slovakia

Location

Cancer Research UK Edinburgh Centre

Edinburgh, Edinburgh, CITY of, EH4 2XR, United Kingdom

Location

St Bartholomew's Hospital

London, London, CITY of, EC1A 7BE, United Kingdom

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

The Christie Hospital NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Liposarcoma; Prostatic Neoplasms; Breast Neoplasms; Adenocarcinoma of Lung; Colorectal Neoplasms

Interventions

Letrozole; Fulvestrant; Midazolam; enzalutamide

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: September 21, 2020
• Study Start: September 23, 2020
• Primary Completion (Estimated): September 23, 2026
• Study Completion (Estimated): November 23, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (4); SL (4); ME (6); CN (5); AR (5); JP (1); CZ (2); US (11)