First-in-Human, Escalating Oral Dose Study of RGT-419B Given Alone and With Endocrine Therapy in Subjects With Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Advanced/Metastatic Breast Cancer
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.
• Eligible subjects must meet all of the following criteria:
‣ Progression after receiving 1 line of prior cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) therapy combined with HT in the MBC setting (up to 1 additional line of CDK4/6i is permitted in the post-surgical adjuvant setting);
∙ Subjects must have received therapy for ≥3 months in the MBC setting, or for ≥6 months in the adjuvant setting, prior to progression
⁃ Progression after ≤3 lines of prior HT therapy (regardless of whether it is HT alone or in combination with other therapies)
∙ Prior HT combination agents, including SERD, SERM or AI, must have received formal approval by regulatory agency.
⁃ ≤ 1 prior line of chemotherapy in the metastatic setting
• Adequate organ function
• Ability to understand and the willingness to sign a written informed consent document