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History of Changes for Study: NCT04606446
Study of PF-07248144 in Advanced or Metastatic Solid Tumors (KAT6)
Latest version (submitted October 10, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 October 22, 2020 None (earliest Version on record)
2 December 4, 2020 Recruitment Status, Study Status, Contacts/Locations, Outcome Measures and Oversight
3 March 4, 2021 Study Status and Contacts/Locations
4 April 12, 2021 Contacts/Locations and Study Status
5 May 28, 2021 Study Status and Contacts/Locations
6 July 27, 2021 Contacts/Locations and Study Status
7 August 17, 2021 Study Status, Contacts/Locations and Study Design
8 November 1, 2021 Study Status and Contacts/Locations
9 January 20, 2022 Contacts/Locations and Study Status
10 August 11, 2022 Contacts/Locations, Arms and Interventions, Outcome Measures, Study Status, Eligibility and Study Description
11 August 20, 2022 Contacts/Locations and Study Status
12 October 10, 2022 Study Status and Contacts/Locations
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Study NCT04606446
Submitted Date:  October 22, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: C4551001
Brief Title: Study of PF-07248144 in Advanced or Metastatic Solid Tumors (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.
Secondary IDs:
Open or close this module Study Status
Record Verification: October 2020
Overall Status: Not yet recruiting
Study Start: November 8, 2020
Primary Completion: September 6, 2024 [Anticipated]
Study Completion: February 8, 2026 [Anticipated]
First Submitted: October 5, 2020
First Submitted that
Met QC Criteria:
October 22, 2020
First Posted: October 28, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
October 22, 2020
Last Update Posted: October 28, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Pfizer
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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.

Open or close this module Conditions
Conditions: 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
Keywords: Solid tumors
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
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.
Number of Arms: 10
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 110 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: 1A Monotherapy Escalation Dose Level 1
PF-07248144 Monotherapy Escalation
Drug: PF-07248144
KAT6 Inhibitor
Experimental: 1A Monotherapy Escalation Dose Level 2
PF-07248144 Monotherapy Escalation
Drug: PF-07248144
KAT6 Inhibitor
Experimental: 1A Monotherapy Escalation Dose Level 3
PF-07248144 Monotherapy Escalation
Drug: PF-07248144
KAT6 Inhibitor
Experimental: 1A Monotherapy Escalation Dose Level 4
PF-07248144 Monotherapy Escalation
Drug: PF-07248144
KAT6 Inhibitor
Experimental: 1B Combination Dose Finding Arm level 1
PF-07248144 with Fulvestrant Combination Dose Finding
Drug: PF-07248144
KAT6 Inhibitor
Drug: Fulvestrant
Endocrine Therapy
Other Names:
  • Faslodex
Experimental: 1B Combination Dose Finding Arm Level 2
PF-07248144 with Fulvestrant Combination Dose Finding
Drug: PF-07248144
KAT6 Inhibitor
Drug: Letrozole
Endocrine Therapy
Other Names:
  • Femara
Drug: Palbociclib
CDK4/6 Inhibitor
Other Names:
  • Ibrance
Experimental: 1C Combination Dose Finding Arm Level 1
PF-07248144 with Letrozole + Palbociclib Combination Dose Finding
Drug: PF-07248144
KAT6 Inhibitor
Experimental: 1C Combination Dose FInding Arm Level 2
PF-07248144 with Letrozole + Palbociclib Combination Dose Finding
Drug: PF-07248144
KAT6 Inhibitor
Drug: Fulvestrant
Endocrine Therapy
Other Names:
  • Faslodex
Drug: Letrozole
Endocrine Therapy
Other Names:
  • Femara
Drug: Palbociclib
CDK4/6 Inhibitor
Other Names:
  • Ibrance
Experimental: 2A Monotherapy Dose Expansion Arm
PF-07248144 Monotherapy Dose Expansion
Drug: PF-07248144
KAT6 Inhibitor
Experimental: 2B Combination Dose Expansion Arm
PF-07248144 with either Fulvestrant or Letrozole + Palbociclib Dose Expansion
Drug: PF-07248144
KAT6 Inhibitor
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of participants with dose-limiting toxicities in the Dose Escalation Arms.
[ Time Frame: Up to 29 days ]

Dose-limiting toxicities (DLTs)
2. 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.
3. 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.
4. 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.
5. 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.
Secondary Outcome Measures:
1. 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
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. Best Overall Response (BOR) in participants in the Dose Escalation Arms
[ Time Frame: Up to 24 months ]

11. Duration of Response (DOR) in participants enrolled in the Dose Escalation Arms
[ Time Frame: Up to 24 months ]

12. 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
13. 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
14. 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.
15. 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.
16. 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.
17. Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms
[ Time Frame: Up to 24 months ]

18. Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms
[ Time Frame: Up to 24 months ]

19. Overall survival (OS) observed in participants enrolled in Dose Expansion Arms
[ Time Frame: Up to 24 months ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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, 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.
Open or close this module Contacts/Locations
Central Contact Person: Pfizer CT.gov Call Center
Telephone: 1-800-718-1021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Study Officials: Pfizer CT.gov Call Center
Study Director
Pfizer
Locations: United States, Texas
NEXT Oncology
San Antonio, Texas, United States, 78229
Open or close this module IPDSharing
Plan to Share IPD: No
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.
Open or close this module References
Citations:
Links: Description: To obtain contact information for a study center near you, click here.
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