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NCT04606446PHASE2Recruiting

Study of PF-07248144 in Advanced or Metastatic Solid Tumors

Pfizer

Start Date

11/16/2020

Completion Date

8/10/2029

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

Detailed Description

Study has two parts, Part 1 (dose escalation) and Part 2 (dose expansion). Part 1 is divided into Parts 1A, 1B, 1C, 1D and 1E and Part 2 is divided into Parts 2A, 2B, 2D and 2E. In Part 1A, single escalating doses of PF-07248144 alone will be administered to determine the maximum tolerable dose (MTD) and select the recommended dose for expansion (RDE). In Part 1B, 1C, 1D and 1E PF-07248144 will be administered in combination with either fulvestrant (Part 1B); palbociclib + letrozole (Part 1C) or PF-07220060+fulvestrant (Part 1D) or vepdegestrant (Part 1E). After the determination of the monotherapy RDE in Part 1A, PF-07248144 will be evaluated in a dose expansion cohort as a monotherapy in Part 2A. After determination of the combination RDE from Part 1B, PF-07248144 in combination with fulvestrant, PF-07248144 will be evaluated in a combination dose expansion with fulvestrant in Part 2B. In Part 1C, PF-07248144 in combination with letrozole + palbociclib will be evaluated for dose finding to determine the MTD and RDE for this combination. After determination of the triple combination RDE from Part 1D, PF-07248144 in combination with PF-07220060 + fulvestrant will be evaluated in a combination dose-expansion cohort, Part 2D. After determination of the combination RDE from Part 1E, PF-07248144 in combination with vepdegestrant will be evaluated in a combination dose-expansion cohort, Part 2E.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

PF-07248144

DRUG

Fulvestrant

DRUG

Letrozole

DRUG

Palbociclib

DRUG

PF-07220060

DRUG

PF-07850327, ARV-471, vepdegestrant

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Conditions

Locally Advanced or Metastatic ER+ HER2- Breast CancerLocally Advanced or Metastatic Castration-resistant Prostate CancerLocally Advanced or Metastatic Non-small Cell Lung Cancer

Locations

HonorHealth

Scottsdale, Arizona 85258

United States

Cedars Sinai Medical Center

Los Angeles, California 90048

United States

Cedars-Sinai Cancer at Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

UCSF Medical Center at Mission Bay

San Francisco, California 94158

United States

Smilow Cancer Hospital at Yale - New Haven

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

New Haven, Connecticut 06511

United States

Holy Cross Hospital

Fort Lauderdale, Florida 33308

United States

St. Elizabeth Healthcare

Edgewood, Kentucky 41017

United States

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

Louisville, Kentucky 40202

United States

University of Louisville

Louisville, Kentucky 40202

United States

UofL Health Brown Cancer Center

Louisville, Kentucky 40202

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

MD Anderson The Woodlands

Conroe, Texas 77384

United States

The University of Texas M. D. Anderson Cancer Center

Houston, Texas 77030

United States

U.T. MD Anderson Cancer Center

Houston, Texas 77030

United States

MD Anderson West Houston

Houston, Texas 77079

United States

MD Anderson League City

League City, Texas 77573

United States

NEXT Oncology

San Antonio, Texas 78229

United States

MD Anderson

Sugar Land, Texas 77478

United States

Swedish Cancer Institute

Seattle, Washington 98104

United States

Swedish Medical Center

Seattle, Washington 98122

United States

Chris O'Brien Lifehouse

Camperdown, New South Wales 2050

Australia

Cancer Research South Australia

Adelaide, South Australia 5000

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Royal Melbourne Hospital

Parkville, Victoria 3050

Australia

Western Health-Sunshine & Footscray Hospitals

St Albans, Victoria 3021

Australia

St. John of God Subiaco Hospital

Subiaco, Western Australia 6008

Australia

Beijing Cancer hospital

Beijing, Beijing Municipality 100142

China

SUN Yat-Sen University Cancer Center

Guangzhou, Guangdong 510060

China

Jilin Province Tumor Hospital

Changchun, Jilin 130000

China

Jilin Province Tumor Hospital

Changchun, Jilin 132000

China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi 710061

China

Aichi Cancer Center Hospital

Nagoya, Aichi-ken 464-8681

Japan

National Cancer Center Hospital East

Kashiwa, Chiba 277-8577

Japan

Kanagawa cancer center

Yokohama, Kanagawa 2418515

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo 104-0045

Japan

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do 13620

South Korea

Seoul National University Hospital

Seoul, Seoul-teukbyeolsi [seoul] 03080

South Korea

Severance Hospital, Yonsei University Health System

Seoul, Seoul-teukbyeolsi [seoul] 03722

South Korea

Samsung Medical Center

Seoul, Seoul-teukbyeolsi [seoul] 06351

South Korea

Kyungpook National University Chilgok Hospital

Daegu, Taegu-kwangyǒkshi 41404

South Korea

Asan Medical Center

Seoul, 05505

South Korea