TrialPath
Recruiting

Study of PF-07248144 in Advanced or Metastatic Solid Tumors

NCT04606446 · Pfizer
In plain English

Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.

Official title
A PHASE 1/2A DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMIC, AND ANTI-TUMOR ACTIVITY OF PF-07248144 IN PARTICIPANTS WITH ADVANCED OR METASTATIC SOLID TUMORS
About this study
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
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 target: 320 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2020-11-16
Estimated completion: 2029-08-10
Last updated: 2026-04-16
Interventions
Drug: PF-07248144Drug: FulvestrantDrug: LetrozoleDrug: PalbociclibDrug: PF-07220060Drug: PF-07850327, ARV-471, vepdegestrant
Primary outcomes
  • Number of participants with dose-limiting toxicities in the Dose Escalation Arms. (Up to 29 days)
  • Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms. (Up to 24 months)
  • Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms. (Up to 24 months)
Sponsor
Pfizer · industry
Contacts & investigators
ContactPfizer CT.gov Call Center · contact · ClinicalTrials.gov_Inquiries@pfizer.com · 1-800-718-1021
InvestigatorPfizer CT.gov Call Center · study_director, Pfizer
All locations (44)
HonorHealthTerminated
Scottsdale, Arizona, United States
Cedars Sinai Medical CenterRecruiting
Los Angeles, California, United States
Cedars-Sinai Cancer at Cedars-Sinai Medical CenterRecruiting
Los Angeles, California, United States
UCSF Medical Center at Mission BayRecruiting
San Francisco, California, United States
Smilow Cancer Hospital at Yale - New HavenRecruiting
New Haven, Connecticut, United States
Yale-New Haven Hospital- Yale Cancer CenterRecruiting
New Haven, Connecticut, United States
Smilow Cancer Hospital Phase 1 UnitRecruiting
New Haven, Connecticut, United States
Yale UniversityRecruiting
New Haven, Connecticut, United States
Holy Cross HospitalTerminated
Fort Lauderdale, Florida, United States
St. Elizabeth HealthcareRecruiting
Edgewood, Kentucky, United States
University Medical Center, lnc.:DBA University of Louisville HospitalRecruiting
Louisville, Kentucky, United States
University of LouisvilleRecruiting
Louisville, Kentucky, United States
UofL Health Brown Cancer CenterRecruiting
Louisville, Kentucky, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
MD Anderson The WoodlandsRecruiting
Conroe, Texas, United States
The University of Texas M. D. Anderson Cancer CenterRecruiting
Houston, Texas, United States
U.T. MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
MD Anderson West HoustonRecruiting
Houston, Texas, United States
MD Anderson League CityRecruiting
League City, Texas, United States
NEXT OncologyRecruiting
San Antonio, Texas, United States
MD AndersonRecruiting
Sugar Land, Texas, United States
Swedish Cancer InstituteRecruiting
Seattle, Washington, United States
Swedish Medical CenterRecruiting
Seattle, Washington, United States
Chris O'Brien LifehouseTerminated
Camperdown, New South Wales, Australia
Cancer Research South AustraliaRecruiting
Adelaide, South Australia, Australia
Peter MacCallum Cancer CentreRecruiting
Melbourne, Victoria, Australia
Royal Melbourne HospitalRecruiting
Parkville, Victoria, Australia
Western Health-Sunshine & Footscray HospitalsRecruiting
St Albans, Victoria, Australia
St. John of God Subiaco HospitalRecruiting
Subiaco, Western Australia, Australia
Beijing Cancer hospitalRecruiting
Beijing, Beijing Municipality, China
SUN Yat-Sen University Cancer CenterRecruiting
Guangzhou, Guangdong, China
Jilin Province Tumor HospitalRecruiting
Changchun, Jilin, China
Jilin Province Tumor HospitalRecruiting
Changchun, Jilin, China
The First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting
Xi'an, Shaanxi, China
Aichi Cancer Center HospitalRecruiting
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital EastRecruiting
Kashiwa, Chiba, Japan
Kanagawa cancer centerRecruiting
Yokohama, Kanagawa, Japan
National Cancer Center HospitalRecruiting
Chuo-ku, Tokyo, Japan
Seoul National University Bundang HospitalRecruiting
Seongnam-si, Gyeonggi-do, South Korea
Seoul National University HospitalRecruiting
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Samsung Medical CenterRecruiting
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Kyungpook National University Chilgok HospitalRecruiting
Daegu, Taegu-kwangyǒkshi, South Korea
Asan Medical CenterRecruiting
Seoul, South Korea
Study of PF-07248144 in Advanced or Metastatic Solid Tumors · TrialPath