This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of RGT-419B administered orally as monotherapy OR in combination with Hormonal Therapy in subjects with HR+, HER2- locally advanced and unresectable (Stage III) or metastatic (Stage IV) breast cancer whose disease has progressed during prior therapy with an approved CDK4/6i plus hormonal therapy.
Male or female >/= 18 years old
ECOG Performance Status 0 to 1
Subjects must have histologically or cytologically confirmed diagnosis of ER+, HER2- ABC consistent with ASCO CAP guidelines that is locally advanced and unresectable (Stage III) or metastatic (Stage IV) BC.
Measurable AND evaluable lesions at baseline per RECIST v1.1.
Presence of visceral metastases with severe organ dysfunction as evidence by signs and symptoms, laboratory studies, lymphangitic spread and/or rapid progression of disease
Pregnant or planning to become pregnant
Prior irradiation to >25% of the bone marrow and/or inadequate bone marrow function or evidence of clinically significant end-organ damage
Major surgery, chemotherapy, targeted therapy, experimental agents, or radiation within 14-28 days prior to Cycle 1, Day 1
Sequential
RGT-419B
Drugoral capsules
RGT-419B in combination with hormonal therapy
DrugRGT-419B in combination with hormonal therapy (Selective Estrogen Receptor Degrader, Selective Estrogen Receptor Modulator, or Aromatase Inhibitor)
Safety & Tolerability - Number of subjects with Dose-Limiting Toxicities (DLTs) at each cohort dose level in singlet and doublet therapy
Number of subjects who have a confirmed DLT at each cohort dose level in singlet and doublet study arms during the first 28-day cycle of RGT-419B treatment.
Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs)
Incidence, severity, and causality of all TEAEs will be assessed for all patient participating from Day 1 dosing through end of study.
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cmax
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve (AUC0-t)
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve to Infinity (AUC0-inf)
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
Symptom Burden
Change from baseline in symptom burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) from baseline to end of treatment
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