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

Plain English Summary

FIH Study of RGT-419B Alone and With Endocrine Therapy in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer is a Phase 1 clinical trial sponsored by Regor Pharmaceuticals Inc. studying Breast Cancer. This trial tests a new oral drug called RGT-419B, alone or with hormone therapy. It is for patients with advanced or metastatic breast cancer that has stopped responding to prior treatments. Participants will take RGT-419B orally, and some will also receive standard hormone therapy. There are no approved alternatives specifically for this stage of cancer after prior treatments. The trial aims to enroll 64 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18 or older with a specific type of breast cancer (ER+, HER2-). Must have advanced or metastatic cancer that has progressed after at least one prior treatment with a CDK4/6 inhibitor and hormone therapy. Cannot have severe organ dysfunction or certain other serious medical conditions. Women who are pregnant or planning to become pregnant cannot participate. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how safe and well-tolerated the new drug is, by tracking any dose-limiting side effects over the first month of treatment. The specific primary outcome measures are: Safety & Tolerability - Number of subjects with Dose-Limiting Toxicities (DLTs) at each cohort dose level in singlet and doublet therapy (4 weeks (1 cycle)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a critical need for new treatments for patients with advanced breast cancer whose disease has become resistant to current therapies. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This Phase 1 trial is an early step to assess a new drug, indicating potential future market entry for a difficult-to-treat cancer subset, with a moderate probability of success given the early stage. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of RGT-419B and hormone therapy. Understand that this is an early-stage trial, and the drug's effectiveness is not yet fully known. Participation involves regular clinic visits for monitoring, blood tests, and drug administration. This trial is currently recruiting participants. The trial is being conducted at 8 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 64 participants

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 Outcomes

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

Secondary Outcomes

• Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs) (through study completion, an average of 1 year)
• Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cmax (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) (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) (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) (through study completion, an average of 1 year)

Full Eligibility Criteria

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

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Hormone Receptor Positive Breast Cancer
• HER2-Negative Breast Cancer
• Metastatic Breast Cancer
• Advanced Breast Cancer
• Endocrine Therapy Resistance
• CDK4/6 Inhibitor Resistance
• ER-Positive Breast Cancer
• Oncology
• Solid Tumors

More Breast Cancer Trials

View all Breast Cancer clinical trials