Study of PF-07224826, as a Single Agent or in Combination With Endocrine Therapy in Participants With Breast Cancer and Other Advanced Solid Tumors.
Breast Cancer, Ovarian Cancer, Liposarcoma
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring 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-)
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Part 1 Dose Escalation-Dose Level 1
Part 1 Dose Escalation-Dose Level 2
Part 1 Dose Escalation-Dose Level 3
Part 1 Dose Escalation-Dose Level 4
Part 1 Dose Escalation-Dose Level 5
Part 2 - Arm A
Part 2 - Arm B
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.
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.
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.
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.
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.
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.
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.