The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

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Molecule overview Clinical trials

Breast Cancer

KAT6 Inhibitor

PF-07248144 is an investigational compound. Its safety and efficacy have not been established.

A Phase 1 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.

Phase 1

NCT04606446

Active enrolling

Locations

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

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Study design Key eligibility criteria Key dates Key endpoints Number of participants Collaborators and investigators

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Study design

Participant Group/Arm

EXPERIMENTAL: 1A Monotherapy Dose Escalation

PF-07248144 Monotherapy Escalation

Intervention/Treatment

DRUG: PF-07248144

KAT6 Inhibitor

Participant Group/Arm

EXPERIMENTAL: 1B Combination Dose Escalation

PF-07248144 with Fulvestrant Combination Dose Escalation

Intervention/Treatment

DRUG: PF-07248144

KAT6 Inhibitor

DRUG: Fulvestrant

Endocrine Therapy

Participant Group/Arm

EXPERIMENTAL: 1C Combination Dose Escalation

PF-07248144 with Letrozole + Palbociclib Combination Dose Escalation

Intervention/Treatment

DRUG: PF-07248144

KAT6 Inhibitor

DRUG: Letrozole

Endocrine Therapy

DRUG: Palbociclib

CDK4/6 Inhibitor

Participant Group/Arm

EXPERIMENTAL: 2A Monotherapy Dose Expansion Arm

PF-07248144 Monotherapy Dose Expansion

Intervention/Treatment

DRUG: PF-07248144

KAT6 Inhibitor

Participant Group/Arm

EXPERIMENTAL: 2B Combination Dose Expansion Arm

PF-07248144 with Fulvestrant Dose Expansion

Intervention/Treatment

DRUG: PF-07248144

KAT6 Inhibitor

DRUG: Fulvestrant

Endocrine Therapy

Participant Group/Arm

EXPERIMENTAL: 1D Combination Dose Escalation

PF-07248144 with PF-07220060 +Fulvestrant

Intervention/Treatment

DRUG: PF-07248144

KAT6 Inhibitor

DRUG: Fulvestrant

Endocrine Therapy

DRUG: PF-07220060

CDK4 inhibitor

Participant Group/Arm

EXPERIMENTAL: 2D Combination Dose Expansion Arm

PF-07248144 with PF-07220060 +Fulvestrant Dose Expansion

Intervention/Treatment

DRUG: PF-07248144

KAT6 Inhibitor

DRUG: Fulvestrant

Endocrine Therapy

DRUG: PF-07220060

CDK4 inhibitor

Participant Group/Arm

EXPERIMENTAL: China Monotherapy Dose Expansion

PF-07248144 Monotherapy Dose Expansion

Intervention/Treatment

DRUG: PF-07248144

KAT6 Inhibitor

Study design table for Clinical Trial

Key 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 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.

Key dates

Study start date

November 2020

Estimated Study Completion Date

May 2025

Key endpoints

Primary Outcome Measures

Outcome Measure

Number of participants with dose-limiting toxicities in the Dose Escalation Arms.

Measure Description

Dose-limiting toxicities (DLTs)

Time Frame

Up to 29 days

Outcome Measure

Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms.

Measure Description

Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

Time Frame

Up to 24 months

Outcome Measure

Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms.

Measure Description

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Time Frame

Up to 24 months

Outcome Measure

Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms

Measure Description

Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

Time Frame

Up to 24 months

Outcome Measure

Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Expansion Arms

Measure Description

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Time Frame

Up to 24 months

Primary Outcome Measures table for Clinical Trial