Study of PF-07248144 in Advanced or Metastatic Solid Tumors

Locally Advanced or Metastatic Non-small Cell Lung Cancer Clinical Trial

— KAT6  

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04606446
• Other study ID #: C4551001
• Status: Recruiting
• Phase: Phase 1
• 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
• 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.

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

External Links

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