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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: D-0502; Drug: palbociclib

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Chaoyang District
    • Beijing, Chaoyang District, China, 100021
      • Local Institution
  • Guangdong
    • Guangzhou, Guangdong, China
      • Local Institution
  • Hunan Provence
    • Changsha, Hunan Provence, China
      • Local Institution
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Local Institution
• United States
  • California
    • Fresno, California, United States, 93720
      • Local Institution
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Local Institution
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Local Institution
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Local Institution
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Local Institution
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Local Institution
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1619
      • Local Institution
  • Texas
    • Dallas, Texas, United States, 75246
      • Local Institution
    • San Antonio, Texas, United States, 78217
      • Local Institution
    • San Antonio, Texas, United States, 78229
      • Local Institution
    • Tyler, Texas, United States, 75702
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically-proven, ER-positive, HER2-negative locally advanced, inoperable, and/or metastatic breast cancer.

2. Female patients with menopausal status:

   i. Postmenopausal status defined as meeting at least one of the following criteria:

   1. Have undergone a bilateral oophorectomy any time in life;
   2. Age ≥60 years, or
   3. 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.

3. Patients meeting all the following criteria:

   1. Has had at least 6 months of endocrine therapy for metastatic ER+ breast cancer prior to disease progression;
   2. Limited number of prior chemotherapy, endocrine therapy, and targeted therapy for advanced or metastatic disease
   3. Radiological or objective evidence of disease progression on or after the last systemic therapy prior to starting current study treatment.
   4. For phase Ia: Not eligible for standard therapy that would confer clinical benefit to the patient.

Exclusion Criteria:

1. Patients with prior anticancer or investigational drug treatment within the following windows are excluded:

2. Participants with prior anticancer or investigational drug treatment within the following windows are excluded:

   1. Any anti-cancer therapy (including endocrine therapy, chemotherapy, targeted therapy, etc.) less than 30 days before first dose of study treatment.
   2. Any investigational drug therapy less than 28 days or 4 half-lives (whichever is shorter) prior to first dose of study treatment.

3. Patients with untreated or symptomatic or progressive central nervous system (CNS) metastases.

   • Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D-0502	Drug: D-0502; oral tablets
Experimental: D-0502 in combination with palbociclib	Drug: D-0502; oral tablets; Drug: palbociclib; standard dose of palbociclib

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: InventisBio Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2018
• Primary Completion (Actual): October 18, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: March 19, 2018
• First Posted (Actual): March 20, 2018

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: IBIO-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No