Study of PF-07248144 in Advanced or Metastatic Solid Tumors
KAT6
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
2 other identifiers
interventional
320
5 countries
44
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2020
Longer than P75 for phase_2
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 5, 2020
CompletedFirst Posted
Study publicly available on registry
October 28, 2020
CompletedStudy Start
First participant enrolled
November 16, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 13, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 10, 2029
April 16, 2026
April 1, 2026
8.7 years
October 5, 2020
April 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Number of participants with dose-limiting toxicities in the Dose Escalation Arms.
Dose-limiting toxicities (DLTs)
Up to 29 days
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
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
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
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 Outcomes (23)
Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms
Up to 24 months
Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms
Up to 24 months
Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms
Up to 24 months
Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms
Up to 24 months
Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms
Up to 24 months
- +18 more secondary outcomes
Study Arms (10)
1A Monotherapy Dose Escalation
EXPERIMENTALPF-07248144 Monotherapy Escalation
1B Combination Dose Escalation
EXPERIMENTALPF-07248144 with Fulvestrant Combination Dose Escalation
1C Combination Dose Escalation
EXPERIMENTALPF-07248144 with Letrozole + Palbociclib Combination Dose Escalation
2A Monotherapy Dose Expansion Arm
EXPERIMENTALPF-07248144 Monotherapy Dose Expansion
2B Combination Dose Expansion Arm
EXPERIMENTALPF-07248144 with Fulvestrant Dose Expansion
1D Combination Dose Escalation
EXPERIMENTALPF-07248144 with PF-07220060 +Fulvestrant
2D Combination Dose Expansion Arm
EXPERIMENTALPF-07248144 with PF-07220060 +Fulvestrant Dose Expansion
China Monotherapy Dose Expansion
EXPERIMENTALPF-07248144 Monotherapy Dose Expansion
1E Combination Dose Escalation
EXPERIMENTALPF-07248144 with Vepdegestrant Combination Dose Escalation
2E Combination Dose Expansion Arm
EXPERIMENTALPF-07248144 with Vepdegestrant Combination Dose Expansion
Interventions
KAT6 Inhibitor
Endocrine Therapy
PROTAC (PROteolysis Targeting Chimera) ER degrader
Eligibility Criteria
You may qualify if:
- 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
- +3 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (44)
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
Related Publications (2)
Mukohara T, Park YH, Sommerhalder D, Yonemori K, Hamilton E, Kim SB, Kim JH, Iwata H, Yamashita T, Layman RM, Mita M, Clay T, Chae YS, Oakman C, Yan F, Kim GM, Im SA, Lindeman GJ, Rugo HS, Liyanage M, Saul M, Le Corre C, Skoura A, Liu L, Li M, LoRusso PM. Inhibition of lysine acetyltransferase KAT6 in ER+HER2- metastatic breast cancer: a phase 1 trial. Nat Med. 2024 Aug;30(8):2242-2250. doi: 10.1038/s41591-024-03060-0. Epub 2024 Jun 1.
PMID: 38824244DERIVEDBishop TR, Subramanian C, Bilotta EM, Garnar-Wortzel L, Ramos AR, Zhang Y, Asiaban JN, Ott CJ, Rock CO, Erb MA. Acetyl-CoA biosynthesis drives resistance to histone acetyltransferase inhibition. Nat Chem Biol. 2023 Oct;19(10):1215-1222. doi: 10.1038/s41589-023-01320-7. Epub 2023 May 1.
PMID: 37127754DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 5, 2020
First Posted
October 28, 2020
Study Start
November 16, 2020
Primary Completion (Estimated)
July 13, 2029
Study Completion (Estimated)
August 10, 2029
Last Updated
April 16, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.