Study of PF-07224826, as a Single Agent or in Combination With Endocrine Therapy in Participants With Breast Cancer and Other Advanced Solid Tumors.

NCT05905341 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: C5331001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Breast Cancer; Ovarian Cancer; Liposarcoma; Non-small Cell Lung Cancer (NSCLC); Endometrial; Solid Tumors

Keywords

cyclin-dependent kinase 2 (CDK2); cyclin-dependent kinase 4 (CDK4); cyclin-dependent kinase 6 (CDK6); hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-)

Outcome Measures

Primary Outcomes (6)

• Part 1: First cycle dose limiting toxicities (DLTs)

  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.

  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

  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.

  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.

  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.

  From the first dose to earliest of 28 days post last dosing date or day of new anticancer therapy -1 day.

Secondary Outcomes (15)

• Part1 and Part 2: Maximum Observed Plasma Concentration (Cmax); Single Dose (SD)

  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)

  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)

  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

  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)

  Cycle 1 (Pre-dose, Day 1, 8, and 15) and Cycle 2 (Day 1). Each cycle is 28 days.

Study Arms (7)

Part 1 Dose Escalation-Dose Level 1

EXPERIMENTAL

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.

Drug: PF-07224826; Combination Product: Fulvestrant

Part 1 Dose Escalation-Dose Level 2

EXPERIMENTAL

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.

Drug: PF-07224826; Combination Product: Fulvestrant

Part 1 Dose Escalation-Dose Level 3

EXPERIMENTAL

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.

Drug: PF-07224826; Combination Product: Fulvestrant

Part 1 Dose Escalation-Dose Level 4

EXPERIMENTAL

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.

Drug: PF-07224826; Combination Product: Fulvestrant

Part 1 Dose Escalation-Dose Level 5

EXPERIMENTAL

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.

Drug: PF-07224826; Combination Product: Fulvestrant

Part 2 - Arm A

EXPERIMENTAL

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.

Drug: PF-07224826; Combination Product: Fulvestrant

Part 2 - Arm B

EXPERIMENTAL

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.

Drug: PF-07224826; Combination Product: Fulvestrant

Interventions

PF-07224826 DRUG

Small molecule cell cycle checkpoint inhibitor that targets CDK 2, 4, and 6, to be administered orally.

Part 1 Dose Escalation-Dose Level 1

Fulvestrant COMBINATION_PRODUCT

Competitive ER antagonist, to be administered by intramuscular injection (prefilled syringe).

Part 1 Dose Escalation-Dose Level 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Liposarcoma; Carcinoma, Non-Small-Cell Lung

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2023
• First Posted: June 15, 2023
• Study Start: January 15, 2024
• Primary Completion: April 14, 2026
• Study Completion (Estimated): April 13, 2028
• Last Updated: November 8, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share