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

Official title

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

Overview

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.

Interventions

• Drug RGT-419B
  oral capsules
• Drug 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)

Primary outcome measures

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

Secondary outcome measures (10)

• Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs) [Time frame: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cmax [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: through study completion, an average of 1 year]
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cumulative urinary excretion [Time frame: through study completion, an average of 1 year]
• Tumor Response assessed by Investigator according to RECIST v1.1 [Time frame: through study completion, an average of 1 year]
• QTc Interval - Changes in corrected QT interval [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• 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

Identifiers

NCT: NCT05304962 · RGT-419B_01-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗