Clinical trial NCT05304962: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Keywords: Breast Cancer
Lead sponsor: Regor Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-31
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: There will be two study arms opened sequentially to the same patient population. Arm A is RGT-419B alone (singlet). Arm B is RGT-419B + Hormonal Therapy (doublet) and will follow completion of Arm A.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety & Tolerability - Number of subjects with Dose-Limiting Toxicities (DLTs) at each cohort dose level in singlet and doublet therapy
timeFrame: 4 weeks (1 cycle)
Secondary outcomes:
measure: Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs)
timeFrame: through study completion, an average of 1 year
measure: Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cmax
timeFrame: through study completion, an average of 1 year
measure: Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve (AUC0-t)
timeFrame: through study completion, an average of 1 year
measure: Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve to Infinity (AUC0-inf)
timeFrame: through study completion, an average of 1 year
measure: Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Plasma Decay Half-Life (t 1/2)
timeFrame: through study completion, an average of 1 year
measure: Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: through study completion, an average of 1 year
measure: Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Accumulation rate after multiple doses
timeFrame: through study completion, an average of 1 year
measure: Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cumulative urinary excretion
timeFrame: through study completion, an average of 1 year
measure: Tumor Response assessed by Investigator according to RECIST v1.1
timeFrame: through study completion, an average of 1 year
measure: QTc Interval - Changes in corrected QT interval
timeFrame: through study completion, an average of 1 year
Other outcomes:
measure: Symptom Burden
timeFrame: through study completion, an average of 1 year
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University California, Los Angeles
state: California
city: Port Saint Lucie
country: United States
facility: Hem-Onc Associates of the Treasure Coast
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood Specialists
state: New York
Study officials:
References: