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

Pfizer

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Breast Cancer Ovarian Cancer Liposarcoma

Interventions

PF-07224826DRUG

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

FulvestrantCOMBINATION_PRODUCT

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

PF-07224826DRUG

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

FulvestrantCOMBINATION_PRODUCT

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

PF-07224826DRUG

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

FulvestrantCOMBINATION_PRODUCT

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

PF-07224826DRUG

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

FulvestrantCOMBINATION_PRODUCT

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

PF-07224826DRUG

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

FulvestrantCOMBINATION_PRODUCT

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

PF-07224826DRUG

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

FulvestrantCOMBINATION_PRODUCT

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

PF-07224826DRUG

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

FulvestrantCOMBINATION_PRODUCT

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Part 1: First cycle dose limiting toxicities (DLTs)

Time frame: 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.

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.

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.

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.

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.