Recruiting
Phase 1
Phase 2

PF-07220060

Sponsor:

Pfizer

Code:

NCT04557449

Conditions

Liposarcoma

Prostate Cancer

Advanced Breast Cancer

NSCLC (Non-small Cell Lung Cancer)

Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

PF-07220060

Letrozole

Fulvestrant

Midazolam

Enzalutamide

Study Details

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 in combination with endocrine therapy.

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.

The Giredestrant Combination Cohort will evaluate PF-07220060 in combination with giredestrant.

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 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 doses of PF-07220060 will be administered in combination with enzalutamide.

In Part 1G, PF-07220060 will be administered in combination with tamoxifen to determine the RDE.

Part 2A is an expansion cohort for PF-07220060 in combination with fulvestrant and will explore more than one dose of PF-07220060.

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

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

Part 2F is an expansion cohort for PF-07220060 in combination with tamoxifen. The Giredestrant Combination Cohort Group A will determine the tolerable dose of PF-07220060 in combination with giredestrant. In Group B, additional participants will be enrolled at the tolerable dose to further assess safety and PK.

The China and Japan monotherapy cohorts will evaluate safety, tolerability, and PK of PF-07220060 as single agent in Chinese and Japanese participants, respectively.

Conditions

Liposarcoma

Prostate Cancer

Advanced Breast Cancer

NSCLC (Non-small Cell Lung Cancer)

Colorectal Cancer

Study ID

NCT04557449

Start date

Sep 23, 2020

Status verified date

Oct, 2026

Completion date

Oct 7, 2029

Anticipated

Primary completion date

Oct 7, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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/Part 1E 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 1G: HR-positive/HER2-negative BC
  • Part 2A, 2B, 2C, 2E, and 2F: HR-positive/HER2-negative BC
  • Part 1D: metastatic castration resistant prostate cancer
  • Giredestrant Combination Cohort: ER-positive/HER2-negative BC
  • 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
  • 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: 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: no 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 1G and 2F: at least 2 lines of SOC for advanced or metastatic disease, including CDK4/6 inhibitor and endocrine therapy
  • Giredestrant Combination Cohort: at least 1 (no more than 3) prior line(s) of SOC for advanced or metastatic disease, including CDK4/6 inhibitor and endocrine therapy

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 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; Part 1G and 2F: tamoxifen treatment within 35 days of Day -4
  • Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
  • Part 1G and 2F: history of or current pulmonary embolism or deep vein thrombosis
  • Giredestrant Combination Cohort: history (within 6 months of screening) of or presence of idiopathic symptomatic bradycardia or resting heart rate <50 bpm at screening
  • 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

Study Design

Enrollment

430 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 1A Monotherapy Escalation Arm 1

PF-07220060 Monotherapy Escalation

experimental: 1A Monotherapy Escalation Arm 2

PF-07220060 Monotherapy Escalation

experimental: 1A Monotherapy Escalation Arm 3

PF-07220060 Monotherapy Escalation

experimental: 1A Monotherapy Escalation Arm 4

PF-07220060 Monotherapy Escalation

experimental: 1A Monotherapy Escalation Arm 5

PF-07220060 Monotherapy Escalation

experimental: 1B Combination Dose Finding Arm 1

PF-07220060 with Letrozole combination Escalation

experimental: 1B Combination Dose Finding Arm 2

PF-07220060 with Letrozole Combination Escalation

experimental: 1C Combination Dose Finding Arm 1

PF-07220060 with Fulvestrant Combination Escalation

experimental: 1C Combination Dose Finding Arm 2

PF-07220060 with Fulvestrant Combination Escalation

experimental: 1D Monotherapy Food Effect

PF-07220060 Monotherapy Food Effect

other: 1E DDI Cohort

PF-07220060 DDI with Midazolam

experimental: 1F Combination Dose Finding

PF-07220060 with Enzalutamide Escalation

experimental: 1G Combination Dose Finding Arm 1

PF-07220060 with Tamoxifen Combination De-Escalation

experimental: 2A Combination Dose Expansion

PF-07220060 with fulvestrant combination expansion

experimental: 2B Combination Dose Expansion

PF-07220060 with Letrozole Combination Expansion

experimental: 2C Combination Dose Expansion

PF-07220060 with fulvestrant Combination Expansion

experimental: 2E Combination Dose Expansion

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

experimental: 2F Combination Dose Expansion

PF-07220060 with Tamoxifen Combination Expansion

experimental: Giredestrant Combination Cohort (Group A)

PF-07220060 with Giredestrant Combination

experimental: Giredestrant Combination Cohort (Group B)

PF-07220060 with Giredestrant Combination

Interventions

PF-07220060

CDK4 inhibitor

Letrozole

Endocrine Therapy

Fulvestrant

Endocrine Therapy

Midazolam

Benzodiazepine

Enzalutamide

Androgen Receptor inhibitor

Giredestrant

Endocrine Therapy

Tamoxifen

Endocrine Therapy

Primary outcome measure

  • Number of participants with dose limiting toxicities in the Dose Escalation or De-escalation Portion [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
  • Incidence of clinically significant AEs [ Time Frame: Cycle 1 (each cycle is 28 days) through study completion, up to approximately 24 months ]
  • Incidence of clinically significant laboratory assessments [ Time Frame: Cycle 1 (each cycle is 28 days) through study completion, up to approximately 24 months ]
  • Incidence of clinically significant abnormal vital and ECG parameters [ Time Frame: Cycle 1 (each cycle is 28 days) through study completion, up to approximately 24 months ]
  • Maximal Plasma Concentration (Cmax) of PF-07220060 given with and without food [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Time to Maximum Plasma Concentration (Tmax) of PF-07220060 given with and without food [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point (AUClast) of PF-07220060 given with and without food [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Maximal Plasma Concentration (Cmax) of Midazolam with and without PF-07220060 [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Time to Maximum Plasma Concentration (Tmax) of Midazolam with and without PF-07220060 [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Timepoint (AUClast) of Midazolam with and without PF-07220060 [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Steady State Maximal Concentration (Cmax,ss) of PF-07220060 [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Steady State Time to Maximum Plasma Concentration (Tmax,ss) of PF-07220060 [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Steady State Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCτ,ss) of PF-07220060 [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Steady State Minimum Plasma Concentration (Cmin,ss) of PF-07220060 [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Steady State Maximal Concentration (Cmax,ss) of Giredestrant [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Steady State Time to Maximum Plasma Concentration (Tmax,ss) of Giredestrant [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Steady State Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCτ,ss) of Giredestrant [ Time Frame: Cycle 1 (each cycle is 28 days) ]
  • Steady State Minimum Plasma Concentration (Cmin,ss) of Giredestrant [ Time Frame: Cycle 1 (each cycle is 28 days) ]

Central Contacts and Locations

Central contacts

Pfizer CT.gov Call Center

1-800-718-1021ClinicalTrials.gov_Inquiries@pfizer.com

Locations

Smilow Cancer Hospital - Yale New Haven Health

Recruiting

New Haven, Connecticut, United States, 06510

Yale-New Haven Hospital-Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06510

Smilow Cancer Hospital Phase 1 Unit

Recruiting

New Haven, Connecticut, United States, 06511

Yale University - Smilow Cancer Hospital; C/O Thomas Ferencz, RPh, BCOP

Recruiting

New Haven, Connecticut, United States, 06511

Smilow Cancer Hospital - Trumbull

Recruiting

Trumbull, Connecticut, United States, 06611

START Midwest

Recruiting

Grand Rapids, Michigan, United States, 49546

Sarah Cannon Research Institute - Pharmacy

Recruiting

Nashville, Tennessee, United States, 37203

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

The University of Texas, MD Anderson Cancer Center - West Houston

Recruiting

Houston, Texas, United States, 77079

More Information

Sponsor

Pfizer

Last update posted

Oct 21, 2026

Last verified

Oct, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-22. This information was provided to ClinicalTrials.gov by Pfizer on 2026-10-21. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.