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

Phase 1

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: RGT-419B in combination with hormonal therapy; Drug: RGT-419B

• Registration Number: NCT05304962
• Lead Sponsor: Regor Pharmaceuticals Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-24
• Study Start: 2022-03-04
• Study First Submitted QC: 2022-03-30
• Study First Posted: 2022-03-31
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-20
• Primary Completion: 2025-12-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. Male or female >/= 18 years old

2. ECOG Performance Status 0 to 1

3. 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.

4. Measurable AND evaluable lesions at baseline per RECIST v1.1.

5. 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

6. Adequate organ function

7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

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
2. Pregnant or planning to become pregnant
3. Prior irradiation to >25% of the bone marrow and/or inadequate bone marrow function or evidence of clinically significant end-organ damage
4. Major surgery, chemotherapy, targeted therapy, experimental agents, or radiation within 14-28 days prior to Cycle 1, Day 1
5. Active, serious medical condition that is not well controlled with locally approved medications allowed by the protocol
6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Arm B	RGT-419B in combination with hormonal therapy	RGT-419B in combination with Hormonal Therapy
Arm A	RGT-419B	RGT-419B given alone as monotherapy

Primary Outcome Measures

Name	Time	Method
Safety & Tolerability - Number of subjects with Dose-Limiting Toxicities (DLTs) at each cohort dose level in singlet and doublet therapy	4 weeks (1 cycle)	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.

Secondary Outcome Measures

Name	Time	Method
Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs)	through study completion, an average of 1 year	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	through study completion, an average of 1 year	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)	through study completion, an average of 1 year	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)	through study completion, an average of 1 year	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 - Plasma Decay Half-Life (t 1/2)	through study completion, an average of 1 year	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 - Time to Reach Maximum Observed Plasma Concentration (Tmax)	through study completion, an average of 1 year	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 - Cumulative urinary excretion	through study completion, an average of 1 year	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
Tumor Response assessed by Investigator according to RECIST v1.1	through study completion, an average of 1 year	Tumor response measured by radiologic imaging techniques at baseline and throughout the study
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Accumulation rate after multiple doses	through study completion, an average of 1 year	Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
QTc Interval - Changes in corrected QT interval	through study completion, an average of 1 year	Number of subjects with a clinically significant increase from baseline in corrected QT (QTc) interval on repeated ECGs during RGT-419B monotherapy.

Trial Locations

Locations (8)

University of California, San Diego; 🇺🇸 La Jolla, California, United States

University California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Hem-Onc Associates of the Treasure Coast; 🇺🇸 Port Saint Lucie, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

New York Cancer and Blood Specialists; 🇺🇸 Port Jefferson Station, New York, United States