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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04606446
Other study ID # C4551001
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date November 16, 2020
Est. completion date November 8, 2026

Study information

Verified date April 2024
Source Pfizer
Contact Pfizer CT.gov Call Center
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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 either fulvestrant or letrozole + palbociclib or with PF-07220060 + fulvestrant


Description:

Study has two parts, Part 1 (dose escalation) and Part 2 (dose expansion). Part 1 is divided into Parts 1A, 1B, 1C and 1D and Part 2 is divided into Parts 2A, 2B and 2D. 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 and 1D, PF-07248144 will be administered in combination with either fulvestrant (Part 1B); palbociclib + letrozole (Part 1C) or PF-07220060+fulvestrant (Part 1D).. 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 186
Est. completion date November 8, 2026
Est. primary completion date May 9, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 and Part 1D (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. - 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


Related Conditions & MeSH terms

  • Carcinoma, Non-Small-Cell Lung
  • Locally Advanced or Metastatic Castration-resistant Prostate Cancer
  • Locally Advanced or Metastatic ER+ HER2- Breast Cancer
  • Locally Advanced or Metastatic Non-small Cell Lung Cancer

Intervention

Drug:
PF-07248144
KAT6 Inhibitor
Fulvestrant
Endocrine Therapy
Letrozole
Endocrine Therapy
Palbociclib
CDK4/6 Inhibitor
PF-07220060
CDK4 inhibitor

Locations

Country Name City State
Australia Cancer Research South Australia Adelaide South Australia
Australia Chris O'Brien Lifehouse Camperdown New South Wales
Australia Peter MacCallum Cancer Centre Melbourne Victoria
Australia Royal Melbourne Hospital Parkville Victoria
Australia Western Health-Sunshine & Footscray Hospitals St Albans Victoria
Australia St. John of God Subiaco Hospital Subiaco Western Australia
China Beijing Cancer hospital Beijing Beijing
China Jilin Cancer Hospital Changchun Jilin
China SUN Yat-Sen University Cancer Center Guangzhou Guangdong
China Hubei Cancer Hospital Wuhan Hubei
China The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi
Japan National Cancer Center Hospital Chuo-ku Tokyo
Japan National Cancer Center Hospital East Kashiwa Chiba
Japan Aichi Cancer Center Hospital Nagoya Aichi
Japan Kanagawa cancer center Yokohama Kanagawa
Korea, Republic of Kyungpook National University Chilgok Hospital Daegu Taegu-kwangyokshi
Korea, Republic of Seoul National University Bundang Hospital Seongnam Ky?nggi-do
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul Seoul-teukbyeolsi [seoul]
Korea, Republic of Seoul National University Hospital Seoul Seoul-teukbyeolsi [seoul]
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul Seoul-teukbyeolsi [seoul]
United States St. Elizabeth Healthcare Edgewood Kentucky
United States Michigan Health Professionals Farmington Hills Michigan
United States Revive Research Institute Farmington Hills Michigan
United States Holy Cross Hospital Fort Lauderdale Florida
United States Holy Cross Hospital Fort Lauderdale Florida
United States Tennessee Oncology PLLC Franklin Tennessee
United States The University of Texas M. D. Anderson Cancer Center Houston Texas
United States U.T. MD Anderson Cancer Center Houston Texas
United States Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute Los Angeles California
United States Cedars-Sinai Medical Center; SOCCI Pharmacy Los Angeles California
United States James Graham Brown Cancer Center Louisville Kentucky
United States University Medical Center, lnc.:DBA University of Louisville Hospital Louisville Kentucky
United States Sarah Cannon Research Institute Nashville Tennessee
United States Tennessee Oncology PLLC Nashville Tennessee
United States The Sarah Cannon Research Institute / Tennessee Oncology, PLLC Nashville Tennessee
United States Smilow Cancer Hospital at Yale - New Haven New Haven Connecticut
United States Smilow Cancer Hospital Phase 1 Unit New Haven Connecticut
United States Yale New Haven Hospital New Haven Connecticut
United States Yale University - Yale Cancer Center New Haven Connecticut
United States Yale-New Haven Hospital New Haven Connecticut
United States Yale-New Haven Hospital- Yale Cancer Center New Haven Connecticut
United States Thomas Jefferson University Philadelphia Pennsylvania
United States Thomas Jefferson University, Bodine Center for Radiation Therapy Philadelphia Pennsylvania
United States Thomas Jefferson University, Clinical Research Unit Philadelphia Pennsylvania
United States Thomas Jefferson University, Gibbon Building Philadelphia Pennsylvania
United States Thomas Jefferson University, Investigational Drug Service Philadelphia Pennsylvania
United States Thomas Jefferson University, Main Office Building Philadelphia Pennsylvania
United States Thomas Jefferson University, Sidney Kimmel Cancer Center Philadelphia Pennsylvania
United States Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization Philadelphia Pennsylvania
United States TJU Research PK/PD Lab Philadelphia Pennsylvania
United States NEXT Oncology San Antonio Texas
United States UCSF Medical Center at Mission Bay San Francisco California
United States HonorHealth Scottsdale Arizona
United States Swedish Cancer Institute Seattle Washington
United States Swedish Medical Center Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  China,  Japan,  Korea, Republic of, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of participants with dose-limiting toxicities in the Dose Escalation Arms. Dose-limiting toxicities (DLTs) Up to 29 days
Primary Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms. Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy. Up to 24 months
Primary Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. Up to 24 months
Primary Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy. Up to 24 months
Primary Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Expansion Arms Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. Up to 24 months
Secondary Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Escalation and Dose Finding Arms Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Multiple Dose: Steady state AUC during a dosage interval (t) (AUCt,ss) in the Dose Escalation and Dose Finding Arms Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Escalation and Dose Finding Arms. Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Escalation and Dose Finding Arms. Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) Up to 24 months
Secondary Palbociclib trough concentrations at steady instate (Cmin,ss) in the 1C combination dose finding arm. Pharmacokinetic (PK) assessment for palbociclib exposure. Up to 24 months
Secondary Best Overall Response (BOR) in participants in the Dose Expansion Arms Up to 24 months
Secondary Duration of Response (DOR) in participants enrolled in the Dose Expansion Arms Up to 24 months
Secondary Peak concentrations of PF-07248144 and PF-07220060 (Part 2D) for selected cycles in the Dose Expansion Arms Pharmacokinetic (PK) assessment for PF-07248144 and PF-07220060 (Part 2D) Up to 24 months
Secondary Trough concentrations of PF-07248144 for selected cycles in the Dose Expansion Arms Pharmacokinetic (PK) assessment for PF-07248144 and PF-07220060 (Part 2D) Up to 24 months
Secondary Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm The effect of food on the PK of PF-07248144. Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Secondary Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm The effect of food on the PK of PF-07248144. Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Secondary AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm The effect of food on the PK of PF 07248144. Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Secondary Amount of PF-07248144 excreted in urine relative to dose administered (%) in a sub-set of participants in monotherapy dose expansion arm. Evaluate urine pharmacokinetic (PK) of PF-07248144. Up to 24 months
Secondary Renal clearance (CLr) in a sub-set of participants in monotherapy dose expansion arm Evaluate urine pharmacokinetic (PK) of PF-07248144. Up to 24 months
Secondary Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms Up to 24 months
Secondary Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms Up to 24 months
Secondary Overall survival (OS) observed in participants enrolled in Dose Expansion Arms Up to 24 months
Secondary Best Overall Response (BOR) observed in participants in the dose expansion arms Up to 24 months
Secondary Duration of Response (DOR) observed in participants in the dose expansion arms up to 24 months
Secondary Clinical Benefit Rate (CBR) observed in participants in the Dose Expansion Arms up to 24 months
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