Clinical trial NCT03471663: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: InventisBio Co., Ltd
Sponsor class: INDUSTRY
First posted: 2018-03-20
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of AEs meeting protocol defined dose-limiting toxicities (DLTs) criteria
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Maximum observed serum concentration (Cmax)
timeFrame: Cycle 1 (28 days)
measure: Area under the serum concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)]
timeFrame: Cycle 1 (28 days)
measure: Time of maximum observed concentration (Tmax)
timeFrame: Cycle 1 (28 days)
measure: Objective response rate (ORR)
timeFrame: up to 12 months
measure: Progression free survival (PFS)
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Local Institution
state: California
city: Aurora
country: United States
facility: Local Institution
state: Colorado
city: New Haven
country: United States
facility: Local Institution
state: Connecticut
city: Boston
country: United States
facility: Local Institution
state: Massachusetts
city: Eugene
country: United States
facility: Local Institution
state: Oregon
city: Greenville
country: United States
facility: Local Institution
state: South Carolina
city: Nashville
country: United States
facility: Local Institution
state: Tennessee
city: Dallas
country: United States
facility: Local Institution
state: Texas
city: San Antonio
country: United States
facility: Local Institution
state: Texas
city: San Antonio
country: United States
facility: Local Institution
state: Texas
city: Tyler
country: United States
facility: Local Institution
state: Texas
city: Beijing
country: China
facility: Local Institution
state: Chaoyang District
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Changsha
country: China
facility: Local Institution
state: Hunan Provence
city: Shenyang
country: China
facility: Local Institution
state: Liaoning
Study officials:
References: