Recruiting
Phase 2

PF-07248144

Sponsor:

Pfizer

Code:

NCT04606446

Conditions

Locally Advanced or Metastatic ER+ HER2- Breast Cancer

Locally Advanced or Metastatic Castration-resistant Prostate Cancer

Locally Advanced or Metastatic Non-small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

PF-07248144

Fulvestrant

Letrozole

Palbociclib

PF-07220060

Study Details

Brief summary:

This is an open-label, multi center study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-07248144 and early signs of clinical efficacy of PF-07248144 as a single agent and in combination with other agents

Conditions

Locally Advanced or Metastatic ER+ HER2- Breast Cancer

Locally Advanced or Metastatic Castration-resistant Prostate Cancer

Locally Advanced or Metastatic Non-small Cell Lung Cancer

Study ID

NCT04606446

Start date

Nov 16, 2020

Status verified date

Apr, 2026

Completion date

Aug 10, 2029

Anticipated

Primary completion date

Jul 13, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Disease Characteristics - Breast, Prostate, and Lung Cancer
  • Part 1A (Monotherapy Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer, CRPC, or NSCLC that is intolerant or resistant to standard therapy or for which no standard therapy is available.
  • Part 1B, Part 1C, Part 1D and Part 1E (Combination Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of treatment with an endocrine therapy and CDK4/6 inhibitor in the advanced or metastatic setting.
  • Part 2A (ER+HER2- breast cancer 2L+, monotherapy) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of CDK4/6 inhibitor and 1 line of endocrine therapy.
  • Part 2B (ER+HER2- breast cancer 2-4L, combination with fulvestrant) Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy.. Participants must not have received more than 3 prior lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have but are not required to have prior treatment with fulvestrant.
  • Part 2D (ER+HER2- breast cancer 2-4L, combination with PF-07220060 (CDK4i) and fulvestrant):

Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy.

  • Participants must have not received more than 3 lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have but are not required to have prior treatment with fulvestrant.
  • Part 2E (ER+HER2- breast cancer 2-4L, combination with vepdegestrant): Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy; Participants must have not received more than 3 lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have received fulvestrant
  • Participants with ER+HER2- advanced or metastatic breast cancer must have documentation of ER-positive tumor (≥1% positive stained cells) based on most recent tumor biopsy utilizing an assay consistent with local standards.
  • Participants with ER+HER2- advanced or metastatic breast cancer must have documentation of HER2-negative tumor: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH/DISH) defined as a HER2/CEP17 ratio <2 or for single probe assessment a HER2 copy number <4.
  • Female participants with ER+HER2- advanced or metastatic breast cancer considered to be of childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause by treatment with the approved LHRH agonist such as goserelin, leuprolide or equivalent agents to induce chemical menopause.
  • Female participants with ER+HER2- advanced or metastatic breast cancer of nonchildbearing potential must meet at least 1 criteria of achieving postmenopausal status.
  • Participants must have at least 1 measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status PS 0 or 1
  • Female or male patients aged ≥ 18 years (Japan ≥ 20 years) (South Korea ≥ 19 years).
  • Adequate renal, liver, and bone marrow function.
  • Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for adverse events (AEs) not constituting a safety risk by investigator judgment.

Exclusion Criteria:

  • Unmanageable ascites (limited medical treatment to control ascites is permitted, but all participants with ascites require review by sponsor's medical monitor).
  • Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
  • Major surgery, radiation therapy, or systemic anti-cancer therapy within 3 weeks prior to study entry.
  • Prior irradiation to >25% of the bone marrow.
  • ECG clinically relevant abnormalities (eg, QTc >470 msec, complete LBBB, second/third degree AV block, ST elevation or EKG changes suggesting myocardial infarction or active myocardia ischemia).
  • Therapeutic anticoagulation. However, low molecular weight heparin is allowed. Vitamin K antagonists or factor Xa inhibitors may be allowed following discussion with the Sponsor.
  • Known or suspected hypersensitivity or severe allergy to active ingredient/excipients of PF-07248144.
  • Active inflammatory GI disease, refractory and unresolved chronic diarrhea or previous gastric resection, lap band surgery or other GI conditions and surgeries that may significantly alter the absorption of PF-07248144 tablets. Gastroesophageal reflux disease under treatment is allowed.
  • Pregnant or breastfeeding female participants.

Study Design

Enrollment

320 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 1A Monotherapy Dose Escalation

PF-07248144 Monotherapy Escalation

experimental: 1B Combination Dose Escalation

PF-07248144 with Fulvestrant Combination Dose Escalation

experimental: 1C Combination Dose Escalation

PF-07248144 with Letrozole + Palbociclib Combination Dose Escalation

experimental: 2A Monotherapy Dose Expansion Arm

PF-07248144 Monotherapy Dose Expansion

experimental: 2B Combination Dose Expansion Arm

PF-07248144 with Fulvestrant Dose Expansion

experimental: 1D Combination Dose Escalation

PF-07248144 with PF-07220060 +Fulvestrant

experimental: 2D Combination Dose Expansion Arm

PF-07248144 with PF-07220060 +Fulvestrant Dose Expansion

experimental: China Monotherapy Dose Expansion

PF-07248144 Monotherapy Dose Expansion

experimental: 1E Combination Dose Escalation

PF-07248144 with Vepdegestrant Combination Dose Escalation

experimental: 2E Combination Dose Expansion Arm

PF-07248144 with Vepdegestrant Combination Dose Expansion

Interventions

PF-07248144

KAT6 Inhibitor

Fulvestrant

Endocrine Therapy

Letrozole

Endocrine Therapy

Palbociclib

CDK4/6 Inhibitor

PF-07220060

CDK4 inhibitor

PF-07850327, ARV-471, vepdegestrant

PROTAC (PROteolysis Targeting Chimera) ER degrader

Primary outcome measure

  • Number of participants with dose-limiting toxicities in the Dose Escalation Arms. [ Time Frame: Up to 29 days ]
  • Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms. [ Time Frame: Up to 24 months ]
  • Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms. [ Time Frame: Up to 24 months ]
  • Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
  • Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]

Central Contacts and Locations

Central contacts

Pfizer CT.gov Call Center

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

Locations

Cedars Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Cedars-Sinai Cancer at Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

UCSF Medical Center at Mission Bay

Recruiting

San Francisco, California, United States, 94158

Smilow Cancer Hospital at Yale - New Haven

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

Recruiting

New Haven, Connecticut, United States, 06511

St. Elizabeth Healthcare

Recruiting

Edgewood, Kentucky, United States, 41017

University Medical Center, lnc.:DBA University of Louisville Hospital

Recruiting

Louisville, Kentucky, United States, 40202

University of Louisville

Recruiting

Louisville, Kentucky, United States, 40202

UofL Health Brown Cancer Center

Recruiting

Louisville, Kentucky, United States, 40202

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

MD Anderson The Woodlands

Recruiting

Conroe, Texas, United States, 77384

The University of Texas M. D. Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

U.T. MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

MD Anderson West Houston

Recruiting

Houston, Texas, United States, 77079

MD Anderson League City

Recruiting

League City, Texas, United States, 77573

NEXT Oncology

Recruiting

San Antonio, Texas, United States, 78229

MD Anderson

Recruiting

Sugar Land, Texas, United States, 77478

Swedish Cancer Institute

Recruiting

Seattle, Washington, United States, 98104

Swedish Medical Center

Recruiting

Seattle, Washington, United States, 98122

More Information

Sponsor

Pfizer

Last update posted

Apr 16, 2026

Last verified

Apr, 2026

Keywords

  • Solid tumors

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Pfizer on 2026-04-16.