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Study of PF-07248144 in Advanced or Metastatic Solid Tumors (KAT6)

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ClinicalTrials.gov Identifier: NCT04606446
Recruitment Status : Recruiting
First Posted : October 28, 2020
Last Update Posted : April 13, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 5, 2020
First Posted Date  ICMJE October 28, 2020
Last Update Posted Date April 13, 2021
Actual Study Start Date  ICMJE November 16, 2020
Estimated Primary Completion Date July 26, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2020)
  • Number of participants with dose-limiting toxicities in the Dose Esclation Arms. [ Time Frame: Up to 29 days ]
    Dose-limiting toxicities (DLTs)
  • Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Esclation Arms. [ Time Frame: Up to 24 months ]
    Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
  • Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Esclation Arms. [ Time Frame: Up to 24 months ]
    Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
  • Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
    Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
  • Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
    Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Original Primary Outcome Measures  ICMJE
 (submitted: October 22, 2020)
  • Number of participants with dose-limiting toxicities in the Dose Escalation Arms. [ Time Frame: Up to 29 days ]
    Dose-limiting toxicities (DLTs)
  • Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms. [ Time Frame: Up to 24 months ]
    Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
  • Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms. [ Time Frame: Up to 24 months ]
    Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
  • Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
    Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
  • Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
    Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2020)
  • Single Dose: Maximum Observed Concentration (Cmax) in the Dose Esclation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Single Dose: Time to Maximum concentration (Tmax) in the Dose Esclation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Esclation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Esclation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Esclation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Esclation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady state AUC during a dosage interval (τ) (AUCτ,ss) in the Dose Esclation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Esclation and Dose Finding Arms. [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Esclation and Dose Finding Arms. [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Best Overall Response (BOR) in participants in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
  • Duration of Respponse (DOR) in participants enrolled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
  • Peak concentrations of PF-07248144 for selected cycles in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessment for PF-07248144
  • Trough concentrations of PF-07248144 for selected cycles in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessment for PF-07248144
  • Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
    The effect of food on the PK of PF-07248144.
  • Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
    The effect of food on the PK of PF-07248144.
  • AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
    The effect of food on the PK of PF 07248144.
  • Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
  • Time to Progression (TTP) observed in participants emrolled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
  • Overall survival (OS) observed in particiapants enrolled in Dose Expansion Arms [ Time Frame: Up to 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2020)
  • Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady state AUC during a dosage interval (τ) (AUCτ,ss) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Escalation and Dose Finding Arms. [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Escalation and Dose Finding Arms. [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessments for PF-07248144
  • Best Overall Response (BOR) in participants in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
  • Duration of Response (DOR) in participants enrolled in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
  • Peak concentrations of PF-07248144 for selected cycles in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessment for PF-07248144
  • Trough concentrations of PF-07248144 for selected cycles in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
    Pharmacokinetic (PK) assessment for PF-07248144
  • Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
    The effect of food on the PK of PF-07248144.
  • Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
    The effect of food on the PK of PF-07248144.
  • AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
    The effect of food on the PK of PF 07248144.
  • Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
  • Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
  • Overall survival (OS) observed in participants enrolled in Dose Expansion Arms [ Time Frame: Up to 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of PF-07248144 in Advanced or Metastatic Solid Tumors
Official Title  ICMJE 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.
Brief 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.
Detailed Description

Study has two parts, Part 1 (dose escalation) and Part 2 (dose expansion). Part 1 is divided into Parts 1A, 1B, and 1C and Part 2 is divided into Parts 2A and 2B. 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 (RP2D). In Part 1B and 1C, PF-07248144 will be administered in combination with either fulvestrant or letrozole + palbociclib.

After the determination of the monotherapy expansion RP2D in Part 1A, PF-07248144 will be evaluated in a dose expansion cohort as a monotherapy in Part 2A. After determination of the combination RP2D from Part 1B and Part 1C, PF-07248144 in combination with an either fulvestrant (Part 1B) or letrozole + palbociclib (Part 1C) may be evaluated in Part 2B. The specific combination partners that will be carried forward to Part 2B will be contingent upon preclinical evidence, clinical safety and potential efficacy as well as PK and PD data.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
The dose escalation parts and the dose finding parts of the study will be guided by a Bayesian analysis of Cycle 1 dose-limiting toxicity (DLT) data for PF-07248144 as monotherapy or in combination with fulvestrant or with letrozole + palbociclib. 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 toxicity relationship of PF-07248144 given in combination with fulvestrant or with letrozole + palbociclib.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Locally Advanced or Metastatic ER+ HER2- Breast Cancer
  • Locally Advanced or Metastatic Castration-resistant Prostate Cancer
  • Locally Advanced or Metastatic Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: PF-07248144
    KAT6 Inhibitor
  • Drug: Fulvestrant
    Endocrine Therapy
    Other Name: Faslodex
  • Drug: Letrozole
    Endocrine Therapy
    Other Name: Femara
  • Drug: Palbociclib
    CDK4/6 Inhibitor
    Other Name: Ibrance
Study Arms  ICMJE
  • Experimental: 1A Monotherapy Escalation Dose Level 1
    PF-07248144 Monotherapy Escalation
    Intervention: Drug: PF-07248144
  • Experimental: 1A Monotherapy Escalation Dose Level 2
    PF-07248144 Monotherapy Escalation
    Intervention: Drug: PF-07248144
  • Experimental: 1A Monotherapy Escalation Dose Level 3
    PF-07248144 Monotherapy Escalation
    Intervention: Drug: PF-07248144
  • Experimental: 1A Monotherapy Escalation Dose Level 4
    PF-07248144 Monotherapy Escalation
    Intervention: Drug: PF-07248144
  • Experimental: 1B Combination Dose Finding Arm level 1
    PF-07248144 with Fulvestrant Combination Dose Finding
    Interventions:
    • Drug: PF-07248144
    • Drug: Fulvestrant
  • Experimental: 1B Combination Dose Finding Arm Level 2
    PF-07248144 with Fulvestrant Combination Dose Finding
    Interventions:
    • Drug: PF-07248144
    • Drug: Letrozole
    • Drug: Palbociclib
  • Experimental: 1C Combination Dose Finding Arm Level 1
    PF-07248144 with Letrozole + Palbociclib Combination Dose Finding
    Intervention: Drug: PF-07248144
  • Experimental: 1C Combination Dose FInding Arm Level 2
    PF-07248144 with Letrozole + Palbociclib Combination Dose Finding
    Interventions:
    • Drug: PF-07248144
    • Drug: Fulvestrant
    • Drug: Letrozole
    • Drug: Palbociclib
  • Experimental: 2A Monotherapy Dose Expansion Arm
    PF-07248144 Monotherapy Dose Expansion
    Intervention: Drug: PF-07248144
  • Experimental: 2B Combination Dose Expansion Arm
    PF-07248144 with either Fulvestrant or Letrozole + Palbociclib Dose Expansion
    Intervention: Drug: PF-07248144
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 22, 2020)
110
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 28, 2025
Estimated Primary Completion Date July 26, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, locally advanced or metastatic CRPC, or locally advanced or metastatic NSCLC that is intolerant or resistant to standard therapy or for which no standard therapy is available.
    • Part 1B and Part 1C (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 3L+, 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 2 lines of endocrine therapy.
    • Part 2B (ER+HER2- breast cancer 2L, combination) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after first line combination treatment with letrozole + palbociclib.
    • 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.
    • 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).
    • 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 4 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Japan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04606446
Other Study ID Numbers  ICMJE C4551001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: 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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP