Study of PF-07248144 in Advanced or Metastatic Solid Tumors (KAT6)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04606446 |
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Recruitment Status :
Recruiting
First Posted : October 28, 2020
Last Update Posted : April 3, 2024
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
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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 or with PF-07220060 + fulvestrant
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Drug: PF-07248144 Drug: Fulvestrant Drug: Letrozole Drug: Palbociclib Drug: PF-07220060 | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 186 participants |
| 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 (Part 1B, Part 1C and Part 1D). 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/DLT relationship of PF-07248144 given in combination with fulvestrant, with letrozole + palbociclib or with PF-07220060 + fulvestrant. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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. |
| Actual Study Start Date : | November 16, 2020 |
| Estimated Primary Completion Date : | May 9, 2025 |
| Estimated Study Completion Date : | November 8, 2026 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: 1A Monotherapy Dose Escalation
PF-07248144 Monotherapy Escalation
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Drug: PF-07248144
KAT6 Inhibitor |
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Experimental: 1B Combination Dose Escalation
PF-07248144 with Fulvestrant Combination Dose Escalation
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Drug: PF-07248144
KAT6 Inhibitor Drug: Fulvestrant Endocrine Therapy
Other Name: Faslodex |
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Experimental: 1C Combination Dose Escalation
PF-07248144 with Letrozole + Palbociclib Combination Dose Escalation
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Drug: PF-07248144
KAT6 Inhibitor Drug: Letrozole Endocrine Therapy
Other Name: Femara Drug: Palbociclib CDK4/6 Inhibitor
Other Name: Ibrance |
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Experimental: 2A Monotherapy Dose Expansion Arm
PF-07248144 Monotherapy Dose Expansion
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Drug: PF-07248144
KAT6 Inhibitor |
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Experimental: 2B Combination Dose Expansion Arm
PF-07248144 with Fulvestrant Dose Expansion
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Drug: PF-07248144
KAT6 Inhibitor Drug: Fulvestrant Endocrine Therapy
Other Name: Faslodex |
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Experimental: 1D Combination Dose Escalation
PF-07248144 with PF-07220060 +Fulvestrant
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Drug: PF-07248144
KAT6 Inhibitor Drug: Fulvestrant Endocrine Therapy
Other Name: Faslodex Drug: PF-07220060 CDK4 inhibitor |
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Experimental: 2D Combination Dose Expansion Arm
PF-07248144 with PF-07220060 +Fulvestrant Dose Expansion
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Drug: PF-07248144
KAT6 Inhibitor Drug: Fulvestrant Endocrine Therapy
Other Name: Faslodex Drug: PF-07220060 CDK4 inhibitor |
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Experimental: China Monotherapy Dose Expansion
PF-07248144 Monotherapy Dose Expansion
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Drug: PF-07248144
KAT6 Inhibitor |
Primary Outcome Measures :
- 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 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.
Secondary Outcome Measures :
- 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 and PF-07220060 (Part 1D)
- 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 and PF-07220060 (Part 1D)
- 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 and PF-07220060 (Part 1D)
- 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 and PF-07220060 (Part 1D)
- 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 and PF-07220060 (Part 1D)
- 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 and PF-07220060 (Part 1D)
- 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 and PF-07220060 (Part 1D)
- 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 and PF-07220060 (Part 1D)
- 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 and PF-07220060 (Part 1D)
- Palbociclib trough concentrations at steady instate (Cmin,ss) in the 1C combination dose finding arm. [ Time Frame: Up to 24 months ]Pharmacokinetic (PK) assessment for palbociclib exposure.
- Best Overall Response (BOR) in participants in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
- Duration of Response (DOR) in participants enrolled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
- Peak concentrations of PF-07248144 and PF-07220060 (Part 2D) for selected cycles in the Dose Expansion Arms [ Time Frame: Up to 24 months ]Pharmacokinetic (PK) assessment for PF-07248144 and PF-07220060 (Part 2D)
- 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 and PF-07220060 (Part 2D)
- 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.
- Amount of PF-07248144 excreted in urine relative to dose administered (%) in a sub-set of participants in monotherapy dose expansion arm. [ Time Frame: Up to 24 months ]Evaluate urine pharmacokinetic (PK) of PF-07248144.
- Renal clearance (CLr) in a sub-set of participants in monotherapy dose expansion arm [ Time Frame: Up to 24 months ]Evaluate urine pharmacokinetic (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 ]
- Best Overall Response (BOR) observed in participants in the dose expansion arms [ Time Frame: Up to 24 months ]
- Duration of Response (DOR) observed in participants in the dose expansion arms [ Time Frame: up to 24 months ]
- Clinical Benefit Rate (CBR) observed in participants in the Dose Expansion Arms [ Time Frame: up to 24 months ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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, 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04606446
Contacts
| Contact: Pfizer CT.gov Call Center | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Locations
Show 56 study locations
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT04606446 |
| Other Study ID Numbers: |
C4551001 |
| First Posted: | October 28, 2020 Key Record Dates |
| Last Update Posted: | April 3, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Pfizer:
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Solid tumors |
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung Neoplasms by Site Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Lung Diseases Respiratory Tract Diseases Letrozole Fulvestrant Palbociclib |
Antineoplastic Agents Aromatase Inhibitors Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Estrogen Receptor Antagonists Protein Kinase Inhibitors |