Study of PF-07248144 in Advanced or Metastatic Solid Tumors
NCT ID: NCT04606446
Last Updated: 2025-08-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
320 participants
INTERVENTIONAL
2020-11-16
2029-09-22
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
A traditional 2-parameter Bayesian Logistic Regression Model (BLRM) will be used to model the DLT relationship of PF-07248144 monotherapy and a more complex BLRM model specifically designed for combinations will be used to model the dose/DLT relationship of PF-07248144 given in combination with fulvestrant, with letrozole + palbociclib, with PF-07220060 + fulvestrant or with vepdegestrant.
TREATMENT
NONE
Study Groups
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1A Monotherapy Dose Escalation
PF-07248144 Monotherapy Escalation
PF-07248144
KAT6 Inhibitor
1B Combination Dose Escalation
PF-07248144 with Fulvestrant Combination Dose Escalation
PF-07248144
KAT6 Inhibitor
Fulvestrant
Endocrine Therapy
1C Combination Dose Escalation
PF-07248144 with Letrozole + Palbociclib Combination Dose Escalation
PF-07248144
KAT6 Inhibitor
Letrozole
Endocrine Therapy
Palbociclib
CDK4/6 Inhibitor
2A Monotherapy Dose Expansion Arm
PF-07248144 Monotherapy Dose Expansion
PF-07248144
KAT6 Inhibitor
2B Combination Dose Expansion Arm
PF-07248144 with Fulvestrant Dose Expansion
PF-07248144
KAT6 Inhibitor
Fulvestrant
Endocrine Therapy
1D Combination Dose Escalation
PF-07248144 with PF-07220060 +Fulvestrant
PF-07248144
KAT6 Inhibitor
Fulvestrant
Endocrine Therapy
PF-07220060
CDK4 inhibitor
2D Combination Dose Expansion Arm
PF-07248144 with PF-07220060 +Fulvestrant Dose Expansion
PF-07248144
KAT6 Inhibitor
Fulvestrant
Endocrine Therapy
PF-07220060
CDK4 inhibitor
China Monotherapy Dose Expansion
PF-07248144 Monotherapy Dose Expansion
PF-07248144
KAT6 Inhibitor
1E Combination Dose Escalation
PF-07248144 with Vepdegestrant Combination Dose Escalation
PF-07248144
KAT6 Inhibitor
PF-07850327, ARV-471, vepdegestrant
PROTAC (PROteolysis Targeting Chimera) ER degrader
2E Combination Dose Expansion Arm
PF-07248144 with Vepdegestrant Combination Dose Expansion
PF-07248144
KAT6 Inhibitor
PF-07850327, ARV-471, vepdegestrant
PROTAC (PROteolysis Targeting Chimera) ER degrader
Interventions
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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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
18 Years
ALL
No
Sponsors
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Pfizer
INDUSTRY
Responsible Party
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Principal Investigators
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Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
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HonorHealth
Scottsdale, Arizona, 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
UCSF Medical Center at Mission Bay
San Francisco, California, United States
Smilow Cancer Hospital at Yale - New Haven
New Haven, Connecticut, United States
Yale-New Haven Hospital- Yale Cancer Center
New Haven, Connecticut, United States
Smilow Cancer Hospital Phase 1 Unit
New Haven, Connecticut, United States
Holy Cross Hospital
Fort Lauderdale, Florida, United States
St. Elizabeth Healthcare
Edgewood, Kentucky, United States
James Graham Brown Cancer Center
Louisville, Kentucky, United States
University Medical Center, lnc.:DBA University of Louisville Hospital
Louisville, Kentucky, United States
Tennessee Oncology PLLC
Franklin, Tennessee, 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
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States
U.T. MD Anderson Cancer Center
Houston, Texas, United States
NEXT Oncology
San Antonio, Texas, United States
Swedish Cancer Institute
Seattle, Washington, United States
Swedish Medical Center
Seattle, Washington, United States
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia
Cancer Research South Australia
Adelaide, South Australia, 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, Australia
Beijing Cancer hospital
Beijing, Beijing Municipality, China
SUN Yat-Sen University Cancer Center
Guangzhou, Guangdong, China
Hubei Cancer Hospital
Wuhan, Hubei, China
Jilin Province Tumor Hospital
Changchun, Jilin, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, China
Aichi Cancer Center Hospital
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, Japan
Kanagawa cancer center
Yokohama, Kanagawa, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan
Seoul National University Bundang Hospital
Seongnam, Ky?nggi-do, South Korea
Seoul National University Hospital
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Severance Hospital, Yonsei University Health System
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Samsung Medical Center
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Kyungpook National University Chilgok Hospital
Daegu, Taegu-kwangyǒkshi, South Korea
Asan Medical Center
Seoul, , South Korea
Countries
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Central Contacts
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References
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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.
Bishop 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.
Related Links
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To obtain contact information for a study center near you, click here.
Other Identifiers
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NCT04606446
Identifier Type: REGISTRY
Identifier Source: secondary_id
C4551001
Identifier Type: -
Identifier Source: org_study_id
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