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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04606446




Registration number
NCT04606446
Ethics application status
Date submitted
5/10/2020
Date registered
28/10/2020

Titles & IDs
Public title
Study of PF-07248144 in Advanced or Metastatic Solid Tumors
Scientific 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.
Secondary ID [1] 0 0
C4551001
Universal Trial Number (UTN)
Trial acronym
KAT6
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic ER+ HER2- Breast Cancer 0 0
Locally Advanced or Metastatic Castration-resistant Prostate Cancer 0 0
Locally Advanced or Metastatic Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-07248144
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Letrozole
Treatment: Drugs - Palbociclib
Treatment: Drugs - PF-07220060

Experimental: 1A Monotherapy Dose Escalation - PF-07248144 Monotherapy Escalation

Experimental: 1B Combination Dose Escalation - PF-07248144 with Fulvestrant Combination Dose Escalation

Experimental: 1C Combination Dose Escalation - PF-07248144 with Letrozole + Palbociclib Combination Dose Escalation

Experimental: 2A Monotherapy Dose Expansion Arm - PF-07248144 Monotherapy Dose Expansion

Experimental: 2B Combination Dose Expansion Arm - PF-07248144 with Fulvestrant Dose Expansion

Experimental: 1D Combination Dose Escalation - PF-07248144 with PF-07220060 +Fulvestrant

Experimental: 2D Combination Dose Expansion Arm - PF-07248144 with PF-07220060 +Fulvestrant Dose Expansion

Experimental: China Monotherapy Dose Expansion - PF-07248144 Monotherapy Dose Expansion


Treatment: Drugs: PF-07248144
KAT6 Inhibitor

Treatment: Drugs: Fulvestrant
Endocrine Therapy

Treatment: Drugs: Letrozole
Endocrine Therapy

Treatment: Drugs: Palbociclib
CDK4/6 Inhibitor

Treatment: Drugs: PF-07220060
CDK4 inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with dose-limiting toxicities in the Dose Escalation Arms.
Timepoint [1] 0 0
Up to 29 days
Primary outcome [2] 0 0
Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms.
Timepoint [2] 0 0
Up to 24 months
Primary outcome [3] 0 0
Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms.
Timepoint [3] 0 0
Up to 24 months
Primary outcome [4] 0 0
Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms
Timepoint [4] 0 0
Up to 24 months
Primary outcome [5] 0 0
Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Expansion Arms
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [2] 0 0
Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms
Timepoint [2] 0 0
Up to 24 months
Secondary outcome [3] 0 0
Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [5] 0 0
Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [6] 0 0
Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Escalation and Dose Finding Arms
Timepoint [6] 0 0
Up to 24 months
Secondary outcome [7] 0 0
Multiple Dose: Steady state AUC during a dosage interval (t) (AUCt,ss) in the Dose Escalation and Dose Finding Arms
Timepoint [7] 0 0
Up to 24 months
Secondary outcome [8] 0 0
Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Escalation and Dose Finding Arms.
Timepoint [8] 0 0
Up to 24 months
Secondary outcome [9] 0 0
Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Escalation and Dose Finding Arms.
Timepoint [9] 0 0
Up to 24 months
Secondary outcome [10] 0 0
Palbociclib trough concentrations at steady instate (Cmin,ss) in the 1C combination dose finding arm.
Timepoint [10] 0 0
Up to 24 months
Secondary outcome [11] 0 0
Best Overall Response (BOR) in participants in the Dose Expansion Arms
Timepoint [11] 0 0
Up to 24 months
Secondary outcome [12] 0 0
Duration of Response (DOR) in participants enrolled in the Dose Expansion Arms
Timepoint [12] 0 0
Up to 24 months
Secondary outcome [13] 0 0
Peak concentrations of PF-07248144 and PF-07220060 (Part 2D) for selected cycles in the Dose Expansion Arms
Timepoint [13] 0 0
Up to 24 months
Secondary outcome [14] 0 0
Trough concentrations of PF-07248144 for selected cycles in the Dose Expansion Arms
Timepoint [14] 0 0
Up to 24 months
Secondary outcome [15] 0 0
Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm
Timepoint [15] 0 0
Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Secondary outcome [16] 0 0
Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm
Timepoint [16] 0 0
Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Secondary outcome [17] 0 0
AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm
Timepoint [17] 0 0
Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Secondary outcome [18] 0 0
Amount of PF-07248144 excreted in urine relative to dose administered (%) in a sub-set of participants in monotherapy dose expansion arm.
Timepoint [18] 0 0
Up to 24 months
Secondary outcome [19] 0 0
Renal clearance (CLr) in a sub-set of participants in monotherapy dose expansion arm
Timepoint [19] 0 0
Up to 24 months
Secondary outcome [20] 0 0
Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms
Timepoint [20] 0 0
Up to 24 months
Secondary outcome [21] 0 0
Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms
Timepoint [21] 0 0
Up to 24 months
Secondary outcome [22] 0 0
Overall survival (OS) observed in participants enrolled in Dose Expansion Arms
Timepoint [22] 0 0
Up to 24 months
Secondary outcome [23] 0 0
Best Overall Response (BOR) observed in participants in the dose expansion arms
Timepoint [23] 0 0
Up to 24 months
Secondary outcome [24] 0 0
Duration of Response (DOR) observed in participants in the dose expansion arms
Timepoint [24] 0 0
up to 24 months
Secondary outcome [25] 0 0
Clinical Benefit Rate (CBR) observed in participants in the Dose Expansion Arms
Timepoint [25] 0 0
up to 24 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/11/2026
Actual
Sample size
Target
186
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Cancer Research South Australia - Adelaide
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [5] 0 0
Western Health-Sunshine & Footscray Hospitals - St Albans
Recruitment hospital [6] 0 0
St. John of God Subiaco Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
3021 - St Albans
Recruitment postcode(s) [6] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Guangdong
Country [13] 0 0
China
State/province [13] 0 0
Hubei
Country [14] 0 0
China
State/province [14] 0 0
Jilin
Country [15] 0 0
China
State/province [15] 0 0
Shaanxi
Country [16] 0 0
Japan
State/province [16] 0 0
Aichi
Country [17] 0 0
Japan
State/province [17] 0 0
Chiba
Country [18] 0 0
Japan
State/province [18] 0 0
Kanagawa
Country [19] 0 0
Japan
State/province [19] 0 0
Tokyo
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Ky?nggi-do
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul-teukbyeolsi [seoul]
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Taegu-kwangyokshi
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
ClinicalTrials.gov_Inquiries@pfizer.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
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.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04606446