G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This is a study to investigate the potential clinical benefit of G1T38 as an oral therapy in combination with fulvestrant in patients with hormone receptor-positive, HER2-negative metastatic breast cancer. The study is an open-label design, consists of 2 parts: dose-finding portion (Part 1), and expansion portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 102 patients will be enrolled in the study.

Official Title
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Phase 1/2 Safety, Pharmacokinetic, and Antitumor Activity Study of G1T38 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer After Endocrine Failure

Conditions
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Carcinoma, Ductal, Breast, Breast Cancer, Breast Neoplasm

Intervention / Treatment
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* Drug: G1T38
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of HR-positive, HER2-negative breast cancer, not amenable to curative therapy Pre- or perimenopausal women can be enrolled if amenable to be treated with goserelin Patients must satisfy 1 of the following criteria for prior therapy: Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor or tamoxifen Progressed during treatment or within 2 months after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer, or prior endocrine therapy for advanced/metastatic breast cancer Received ≤ 2 chemotherapy regimens (Part 1) or ≤ 1 chemotherapy regimen (Part 2) for advanced/metastatic disease For Part 1, evaluable or measurable disease (bone only disease eligible for Part 1 only) For Part 2, measurable disease as defined by RECIST, Version 1.1 ECOG performance status 0 to 1 Adequate organ function Exclusion Criteria: For Part 1, prior treatment with fulvestrant For Part 2, prior treatment with any CDK inhibitor or fulvestrant Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease Chemotherapy within 21 days of first G1T38 dose Investigational drug within 28 days of first G1T38 dose Concurrent radiotherapy, radiotherapy within 14 days of first G1T38 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow Prior hematopoietic stem cell or bone marrow transplantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Once-Daily G1T38 Dosing<br>G1T38 (lerociclib) orally (once daily) in combination with fulvestrant. | Drug: G1T38<br> <br> * Other names: lerociclib;Drug: Fulvestrant<br> <br> * Other names: Faslodex;|
| Experimental: Twice-Daily G1T38 Dosing<br>G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant. | Drug: G1T38<br> <br> * Other names: lerociclib;Drug: Fulvestrant<br> <br> * Other names: Faslodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity |  | Week 1 Day 1-Week 5 Day 1 | 
| Recommended Phase 2 dose |  | 14 months | 
| Recommended Phase 2 dose interval | Twice-Daily or Once-Daily dosing | 14 months | 
| Number of Treatment Related Adverse Event, including Abnormal Laboratory Events | All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug from the signing of the informed consent until 30 days after the last dose of study medication up to 36 months | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response based on RECIST, Version 1.1 |  | 30 months | 
| Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax) |  | Week 1 Day 1-Week 9 Day 1 | 
| Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC) |  | Week 1 Day 1-Week 9 Day 1 | 
| Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2) |  | Week 1 Day 1-Week 9 Day 1 | 
| Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution |  | Week 1 Day 1-Week 9 Day 1 | 
| Progression free survival (PFS) |  | 36 months | 
| Overall survival (OS) |  | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HR+, HER2-, Breast Cancer, CDK 4/6 Inhibitor, HER2-Negative, HR-Positive, HER2 -ve, HER2 +ve