FIH Study of RGT-419B Alone and With Endocrine Therapy in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer

Официальное название

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

Обзор

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.

Вмешательства

• Препарат RGT-419B
  oral capsules
• Препарат RGT-419B in combination with hormonal therapy
  RGT-419B in combination with hormonal therapy (Selective Estrogen Receptor Degrader, Selective Estrogen Receptor Modulator, or Aromatase Inhibitor)

Первичные конечные точки

• Safety & Tolerability - Number of subjects with Dose-Limiting Toxicities (DLTs) at each cohort dose level in singlet and doublet therapy [Срок оценки: 4 weeks (1 cycle)]

Вторичные конечные точки (10)

• Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs) [Срок оценки: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cmax [Срок оценки: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve (AUC0-t) [Срок оценки: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve to Infinity (AUC0-inf) [Срок оценки: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Plasma Decay Half-Life (t 1/2) [Срок оценки: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Time to Reach Maximum Observed Plasma Concentration (Tmax) [Срок оценки: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Accumulation rate after multiple doses [Срок оценки: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cumulative urinary excretion [Срок оценки: through study completion, an average of 1 year]
• Tumor Response assessed by Investigator according to RECIST v1.1 [Срок оценки: through study completion, an average of 1 year]
• QTc Interval - Changes in corrected QT interval [Срок оценки: through study completion, an average of 1 year]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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
• Active, serious medical condition that is not well controlled with locally approved medications allowed by the protocol
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• University of California, San Diego — La Jolla
• University California, Los Angeles — Los Angeles
• Hem-Onc Associates of the Treasure Coast — Port Saint Lucie
• Moffitt Cancer Center — Tampa
• Emory University — Atlanta
• Massachusetts General Hospital — Boston
• Washington University School of Medicine — St Louis
• New York Cancer and Blood Specialists — Port Jefferson Station

Идентификаторы

NCT: NCT05304962 · RGT-419B_01-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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