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

Primary Purpose

Breast Cancer

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

RGT-419B

RGT-419B in combination with hormonal therapy

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female >/= 18 years old
ECOG Performance Status 0 to 1
HR+, HER2- tumor by most recent biopsy with measurable disease
Have had no more than 1 prior line of cytotoxic chemotherapy in the ABC setting AND no serious/severe toxicity to a prior CKD4/6i AND no known contraindication to receiving RT-419B AND have had all acute/residual toxic effects of any prior therapy
In the ABC setting, eligible subjects must have failed to respond to or progressed after <3 lines of prior CDK4/6i therapy and unlimited lines of prior HT and have had no more than 1 prior line of chemotherapy. Eligible subjects must have received and progressed on any combination of HTs including any approved AI, SERD, or SERM, and/or any approved CDK4/6i in any order.

(5a) For subjects in Arm B, at least one line of prior therapy must have included a locally approved HT which was well tolerated and which the subject is willing to receive again (5b) Subjects with tumors harboring a PIK3CA mutation will be allowed to enroll, and treatment with a PI3Ki in combination with HT will be allowed as a prior line of therapy. Surgical excision of tumor tissue accompanied by chemotherapy or targeted therapy is also counted as 1 line of prior treatment.

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 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

Sites / Locations

Hem-Onc Associates of the Treasure CoastRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm A

Arm B

Arm Description

RGT-419B given alone as monotherapy

RGT-419B in combination with Hormonal Therapy

Outcomes

Primary Outcome Measures

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

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

Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs)

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

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)

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)

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)

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)

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 - Accumulation rate after multiple doses

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

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

Tumor response measured by radiologic imaging techniques at baseline and throughout the study

QTc Interval - Changes in corrected QT interval

Number of subjects with a clinically significant increase from baseline in corrected QT (QTc) interval on repeated ECGs during RGT-419B monotherapy.

Full Information

NCT ID

NCT05304962

First Posted

February 24, 2022

Last Updated

October 11, 2023

Sponsor

Regor Pharmaceuticals Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05304962

Brief Title

First-in-Human Study of RGT-419B Alone and With Endocrine Therapy in Subjects With 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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 4, 2022 (Actual)

Primary Completion Date

February 28, 2024 (Anticipated)

Study Completion Date

August 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regor Pharmaceuticals Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

RGT-419B given alone as monotherapy

Arm Title

Arm B

Arm Type

Experimental

Arm Description

RGT-419B in combination with Hormonal Therapy

Intervention Type

Drug

Intervention Name(s)

RGT-419B

Intervention Description

oral capsules

Intervention Type

Drug

Intervention Name(s)

RGT-419B in combination with hormonal therapy

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

4 weeks (1 cycle)

Secondary Outcome Measure Information:

Title

Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs)

Description

Incidence, severity, and causality of all TEAEs will be assessed for all patient participating from Day 1 dosing through end of study.

Time Frame

through study completion, an average of 1 year

Title

Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cmax

Description

Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification

Time Frame

through study completion, an average of 1 year

Title

Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve (AUC0-t)

Description

Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification

Time Frame

through study completion, an average of 1 year

Title

Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve to Infinity (AUC0-inf)

Description

Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification

Time Frame

through study completion, an average of 1 year

Title

Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Plasma Decay Half-Life (t 1/2)

Description

Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification

Time Frame

through study completion, an average of 1 year

Title

Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Time to Reach Maximum Observed Plasma Concentration (Tmax)

Description

Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification

Time Frame

through study completion, an average of 1 year

Title

Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Accumulation rate after multiple doses

Description

Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification

Time Frame

through study completion, an average of 1 year

Title

Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cumulative urinary excretion

Description

Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification

Time Frame

through study completion, an average of 1 year

Title

Tumor Response assessed by Investigator according to RECIST v1.1

Description

Tumor response measured by radiologic imaging techniques at baseline and throughout the study

Time Frame

through study completion, an average of 1 year

Title

QTc Interval - Changes in corrected QT interval

Description

Number of subjects with a clinically significant increase from baseline in corrected QT (QTc) interval on repeated ECGs during RGT-419B monotherapy.

Time Frame

through study completion, an average of 1 year

Other Pre-specified Outcome Measures:

Title

Symptom Burden

Description

Change from baseline in symptom burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) from baseline to end of treatment

Time Frame

through study completion, an average of 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female >/= 18 years old ECOG Performance Status 0 to 1 HR+, HER2- tumor by most recent biopsy with measurable disease Have had no more than 1 prior line of cytotoxic chemotherapy in the ABC setting AND no serious/severe toxicity to a prior CKD4/6i AND no known contraindication to receiving RT-419B AND have had all acute/residual toxic effects of any prior therapy In the ABC setting, eligible subjects must have failed to respond to or progressed after <3 lines of prior CDK4/6i therapy and unlimited lines of prior HT and have had no more than 1 prior line of chemotherapy. Eligible subjects must have received and progressed on any combination of HTs including any approved AI, SERD, or SERM, and/or any approved CDK4/6i in any order. (5a) For subjects in Arm B, at least one line of prior therapy must have included a locally approved HT which was well tolerated and which the subject is willing to receive again (5b) Subjects with tumors harboring a PIK3CA mutation will be allowed to enroll, and treatment with a PI3Ki in combination with HT will be allowed as a prior line of therapy. Surgical excision of tumor tissue accompanied by chemotherapy or targeted therapy is also counted as 1 line of prior treatment. 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 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Regor Central Office

Phone

617-315-9070

rgt-419b_01-101@regor.com

Facility Information:

Facility Name

Hem-Onc Associates of the Treasure Coast

City

Port Saint Lucie

State/Province

Florida

ZIP/Postal Code

34952

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Heather Yeckes-Rodin, MD

Phone

772-335-5666

12. IPD Sharing Statement

Learn more about this trial

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

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