A First-in-Human Study of D-0502 Alone and in Combination With Palbociclib in Women With Advanced or Metastatic ER-Positive and HER2-Negative Breast Cancer

Study Overview
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Brief Summary
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This is a phase I, open-label study of D-0502 single agent and D-0502 in combination with standard dose of palbociclib to assess the safety and tolerability, identify an MTD, and/or RP2D, evaluate the PK properties and evaluate preliminary anti-tumor activities in women with advanced or metastatic ER-positive, HER2-negative breast cancer.

Official Title
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A Phase I, Open-Label Study of D-0502 Single Agent and D-0502 in Combination With Palbociclib in Women With Advanced or Metastatic ER-Positive and HER2-Negative Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: D-0502
* Drug: palbociclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-proven, ER-positive, HER2-negative locally advanced, inoperable, and/or metastatic breast cancer. Female patients with menopausal status: i. Postmenopausal status defined as meeting at least one of the following criteria: Have undergone a bilateral oophorectomy any time in life; Age ≥60 years, or Age <60 years but have cessation of regular menses ≥12 months with follicle stimulating hormone (FSH) value >40 milli-international units per milliliter (mIU/mL) and an estradiol value <40 picograms per milliliter (pg/mL) (140 picomoles per liter [pmol/L]). ii. Premenopausal or perimenopausal concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 4 weeks before the start of trial therapy and is planned to continue LHRH agonist during the study. Patients meeting all the following criteria: Has had at least 6 months of endocrine therapy for metastatic ER+ breast cancer prior to disease progression; Limited number of prior chemotherapy, endocrine therapy, and targeted therapy for advanced or metastatic disease Radiological or objective evidence of disease progression on or after the last systemic therapy prior to starting current study treatment. For phase Ia: Not eligible for standard therapy that would confer clinical benefit to the patient. Exclusion Criteria: Patients with prior anticancer or investigational drug treatment within the following windows are excluded: Participants with prior anticancer or investigational drug treatment within the following windows are excluded: Any anti-cancer therapy (including endocrine therapy, chemotherapy, targeted therapy, etc.) less than 30 days before first dose of study treatment. Any investigational drug therapy less than 28 days or 4 half-lives (whichever is shorter) prior to first dose of study treatment. Patients with untreated or symptomatic or progressive central nervous system (CNS) metastases. Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D-0502<br>D-0502 | Drug: D-0502<br>* oral tablets<br>|
| Experimental: D-0502 in combination with palbociclib<br>D-0502 in combination with palbociclib | Drug: D-0502<br>* oral tablets<br>Drug: palbociclib<br>* standard dose of palbociclib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs meeting protocol defined dose-limiting toxicities (DLTs) criteria |  | Approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) |  | Cycle 1 (28 days) | 
| Area under the serum concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] |  | Cycle 1 (28 days) | 
| Time of maximum observed concentration (Tmax) |  | Cycle 1 (28 days) | 
| Objective response rate (ORR) |  | up to 12 months | 
| Progression free survival (PFS) |  | up to 12 months |