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
Geo Regions
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
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
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 primary completion date
- November 2026
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
Secondary Outcome Measures:
Outcome Measure
Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Escalation and Dose Finding Arms
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Multiple Dose: Steady state AUC during a dosage interval (τ) (AUCτ,ss) in the Dose Escalation and Dose Finding Arms
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Escalation and Dose Finding Arms.
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Escalation and Dose Finding Arms.
Measure Description
Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D)
Time Frame
Up to 24 months
Outcome Measure
Palbociclib trough concentrations at steady instate (Cmin,ss) in the 1C combination dose finding arm.
Measure Description
Pharmacokinetic (PK) assessment for palbociclib exposure.
Time Frame
Up to 24 months
Outcome Measure
Best Overall Response (BOR) in participants in the Dose Expansion Arms
Time Frame
Up to 24 months
Outcome Measure
Duration of Response (DOR) in participants enrolled in the Dose Expansion Arms
Time Frame
Up to 24 months
Outcome Measure
Peak concentrations of PF-07248144 and PF-07220060 (Part 2D) for selected cycles in the Dose Expansion Arms
Measure Description
Pharmacokinetic (PK) assessment for PF-07248144 and PF-07220060 (Part 2D)
Time Frame
Up to 24 months
Outcome Measure
Trough concentrations of PF-07248144 for selected cycles in the Dose Expansion Arms
Measure Description
Pharmacokinetic (PK) assessment for PF-07248144 and PF-07220060 (Part 2D)
Time Frame
Up to 24 months
Outcome Measure
Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm
Measure Description
The effect of food on the PK of PF-07248144.
Time Frame
Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Outcome Measure
Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm
Measure Description
The effect of food on the PK of PF-07248144.
Time Frame
Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Outcome Measure
AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm
Measure Description
The effect of food on the PK of PF 07248144.
Time Frame
Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Outcome Measure
Amount of PF-07248144 excreted in urine relative to dose administered (%) in a sub-set of participants in monotherapy dose expansion arm.
Measure Description
Evaluate urine pharmacokinetic (PK) of PF-07248144.
Time Frame
Up to 24 months
Outcome Measure
Renal clearance (CLr) in a sub-set of participants in monotherapy dose expansion arm
Measure Description
Evaluate urine pharmacokinetic (PK) of PF-07248144.
Time Frame
Up to 24 months
Outcome Measure
Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms
Time Frame
Up to 24 months
Outcome Measure
Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms
Time Frame
Up to 24 months
Outcome Measure
Overall survival (OS) observed in participants enrolled in Dose Expansion Arms
Time Frame
Up to 24 months
Outcome Measure
Best Overall Response (BOR) observed in participants in the dose expansion arms
Time Frame
Up to 24 months
Outcome Measure
Duration of Response (DOR) observed in participants in the dose expansion arms
Time Frame
up to 24 months
Outcome Measure
Clinical Benefit Rate (CBR) observed in participants in the Dose Expansion Arms
Time Frame
up to 24 months
Number of participants
186
Collaborators and investigators
Sponsor: Pfizer
Collaborator: None