study of pf-07224826, as a single agent or in combination with endocrine therapy in participants with breast cancer and other advanced solid tumors.

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

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.


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.

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-)