Study of PF-07224826, as a Single Agent or in Combination With Endocrine Therapy in Participants With Breast Cancer and Other Advanced Solid Tumors.
November 6, 2023 updated by: Pfizer
A PHASE 1, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07224826, AS A SINGLE AGENT AND IN COMBINATION WITH ENDOCRINE THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
This is a Phase 1, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of PF-07224826, as a single agent or in combination with endocrine therapy in participants with advanced solid tumors. This study will be divided into dose escalation/finding (Part 1) and dose expansion (Part 2).
In Part 1, participants with locally recurrent/advanced or metastatic Triple Negative Breast Cancer (TNBC), platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent. Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy.
In Part 2 (Arm A), PF-07224826 will be evaluated in combination with fulvestrant in HR-positive HER2-negative advanced or mBC participants who have received prior CDK4/6 inhibitor. In Part 2 (Arm B), PF-07224826 will be evaluated in combination with fulvestrant in HR-positive HER2-negative locally advanced or mBC participants whose disease has progressed on prior endocrine therapy and is naïve to CDK4/6 inhibitors.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
Part 1:
- Participants with HR-positive HER2-negative locally advanced or metastatic breast cancer.
- Participants with locally recurrent/advanced or metastatic TNBC.
- Participants with advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC).
- Other advanced solid tumor types: Tumors other than BC or Ovarian: NSCLC, prostate, endometrial, liposarcoma, or other tumors with cyclin D (CCND) and cyclin E (CCNE) implicated in pathogenesis either by gene amplification or overexpression.
- Part 2 (Arm A): Participants with HR positive HER2 negative locally advanced or mBC (post CDK4/6 inhibitors).
- Part 2 (Arm B): Participants with HR positive HER2 negative locally advanced or mBC (naïve to CDK4/6 inhibitors).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
- Adequate Bone Marrow Function
Exclusion Criteria:
- Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, Cerebral edema, and/or progressive growth. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before enrollment and have no evidence of progression at time of study enrollment.
- Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (eg, including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
- 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.
- Last anticancer treatment within 2 weeks (or 5 half-lives, whichever is shorter), unless the last immediate anticancer treatment contained an antibody-based agent(s) (approved or investigational), then the interval of 4 weeks or 5 half-lives (whichever is shorter) is required prior to receiving the study intervention.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Part 1 Dose Escalation-Dose Level 1
In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent.
Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy.
PF-07224826 will be administered orally, once daily, on a continuous basis.
|
Small molecule cell cycle checkpoint inhibitor that targets CDK 2, 4, and 6, to be administered orally.
Competitive ER antagonist, to be administered by intramuscular injection (prefilled syringe).
|
|
Experimental: Part 1 Dose Escalation-Dose Level 2
In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent.
Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy.
PF-07224826 will be administered orally, once daily, on a continuous basis.
|
Small molecule cell cycle checkpoint inhibitor that targets CDK 2, 4, and 6, to be administered orally.
Competitive ER antagonist, to be administered by intramuscular injection (prefilled syringe).
|
|
Experimental: Part 1 Dose Escalation-Dose Level 3
In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent.
Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy.
PF-07224826 will be administered orally, once daily, on a continuous basis.
|
Small molecule cell cycle checkpoint inhibitor that targets CDK 2, 4, and 6, to be administered orally.
Competitive ER antagonist, to be administered by intramuscular injection (prefilled syringe).
|
|
Experimental: Part 1 Dose Escalation-Dose Level 4
In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent.
Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy.
PF-07224826 will be administered orally, once daily, on a continuous basis.
|
Small molecule cell cycle checkpoint inhibitor that targets CDK 2, 4, and 6, to be administered orally.
Competitive ER antagonist, to be administered by intramuscular injection (prefilled syringe).
|
|
Experimental: Part 1 Dose Escalation-Dose Level 5
In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent.
Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy.
PF-07224826 will be administered orally, once daily, on a continuous basis.
|
Small molecule cell cycle checkpoint inhibitor that targets CDK 2, 4, and 6, to be administered orally.
Competitive ER antagonist, to be administered by intramuscular injection (prefilled syringe).
|
|
Experimental: Part 2 - Arm A
In Part 2 Arm A, PF-07224826 will be evaluated in combination with fulvestrant in HR positive HER2 negative advanced or mBC participants who have received prior CDK4/6 inhibitor.
PF-07224826 will be administered orally, once daily, on a continuous basis.
|
Small molecule cell cycle checkpoint inhibitor that targets CDK 2, 4, and 6, to be administered orally.
Competitive ER antagonist, to be administered by intramuscular injection (prefilled syringe).
|
|
Experimental: Part 2 - Arm B
In Part 2 Arm B, PF-07224826 will be evaluated in combination with fulvestrant in HR-positive HER2-negative locally advanced or mBC participants whose disease has progressed on prior endocrine therapy and is naïve to CDK4/6 inhibitors.
PF-07224826 will be administered orally, once daily, on a continuous basis.
|
Small molecule cell cycle checkpoint inhibitor that targets CDK 2, 4, and 6, to be administered orally.
Competitive ER antagonist, to be administered by intramuscular injection (prefilled syringe).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Part 1: First cycle dose limiting toxicities (DLTs)
Time Frame: Cycle 1 (28 days)
|
Cycle 1 (28 days)
|
|
Part 1 and Part 2: Adverse events (AEs) as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0), timing, seriousness and relationship to study therapy.
Time Frame: From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.
|
From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.
|
|
Part 1 and Part 2: Number of participants with Clinical Laboratory abnormalities
Time Frame: From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.
|
From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.
|
|
Part 1 and Part 2: Incidence of clinically significant abnormal vital signs.
Time Frame: From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.
|
From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.
|
|
Part 2: Preliminary antitumor activity measure for efficacy includes ORR, as assessed using RECIST version 1.1.
Time Frame: From baseline until the date of first documented progression, or date of death of any cause, or date of withdrawal of consent, or date of lost to follow-up, whichever came first.
|
From baseline until the date of first documented progression, or date of death of any cause, or date of withdrawal of consent, or date of lost to follow-up, whichever came first.
|
|
Part 1 and Part 2: Incidence of clinically significant abnormal ECGs.
Time Frame: From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.
|
From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Part1 and Part 2: Maximum Observed Plasma Concentration (Cmax); Single Dose (SD)
Time Frame: Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
|
Part 1 and Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax); Single Dose (SD)
Time Frame: Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
|
Part 1: Area under the concentration-time curve from 0 to time of last measurable concentration (AUClast)
Time Frame: Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
|
Part 1 and Part 2: Maximum Observed Plasma concentration (Cmax,ss), steady state
Time Frame: Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
|
Part 1 and Part 2: Time to Reach Maximum Observed Plasma Concentration steady state (Tmax, ss)
Time Frame: Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
|
Part 1 and Part 2: Minimum Observed Plasma Concentration (Cmin, ss), steady state
Time Frame: Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
|
Part 1: Area Under the concentration-time curve from 0 to time the end of the dosing interval (AUCtau,ss), steady state
Time Frame: Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
|
Part 2: Accumulation ratio (Rac)
Time Frame: Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.
|
|
Part 1: Objective Response, as assessed using RECIST version 1.1.
Time Frame: From baseline and up to approximately 24 months
|
From baseline and up to approximately 24 months
|
|
Part 1 and Part 2: Duration of Response (DoR) of PF-07224826 alone or in combination with fulvestrant
Time Frame: From baseline and up to approximately 24 months
|
From baseline and up to approximately 24 months
|
|
Part 1 and Part 2: Progression-Free Survival (PFS) of PF-07224826 alone or in combination with fulvestrant
Time Frame: From baseline and up to approximately 24 months
|
From baseline and up to approximately 24 months
|
|
Part 1 and Part 2: Time to Response (TTR) of PF-07224826 alone or in combination with fulvestrant
Time Frame: From baseline and up to approximately 24 months
|
From baseline and up to approximately 24 months
|
|
Part 2: Overall Survival (OS) of PF-07224826 with fulvestrant
Time Frame: From baseline and up to approximately 24 months
|
From baseline and up to approximately 24 months
|
|
Part 2: Clinical benefit response (CBR) of PF-07224826 with fulvestrant
Time Frame: From baseline and up to approximately 24 months
|
From baseline and up to approximately 24 months
|
|
Part 1 and Part 2: Expression of Pharmacodynamic (PD) biomarkers in tumor tissue
Time Frame: From baseline and up to approximately 24 months
|
From baseline and up to approximately 24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Estimated)
January 15, 2024
Primary Completion (Estimated)
April 14, 2026
Study Completion (Estimated)
April 13, 2028
Study Registration Dates
First Submitted
May 24, 2023
First Submitted That Met QC Criteria
June 7, 2023
First Posted (Actual)
June 15, 2023
Study Record Updates
Last Update Posted (Actual)
November 8, 2023
Last Update Submitted That Met QC Criteria
November 6, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Sarcoma
- Neoplasms, Adipose Tissue
- Breast Neoplasms
- Liposarcoma
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Estrogen Antagonists
- Estrogen Receptor Antagonists
- Fulvestrant
Other Study ID Numbers
- C5331001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD 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.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.