To Evaluate the Safety, Tolerability, and Pharmacokinetics of GDC-0077 Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer

Status: Active

Description

This is an open-label, multicenter, Phase I study designed to evaluate the safety, tolerability, and pharmacokinetics of GDC-0077 administered orally as a single agent in participants with locally advanced or metastatic Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA)-mutant solid tumors, including breast cancer, and in combination with standard-of-care endocrine and targeted therapies for the treatment of locally advanced or metastatic PIK3CA-mutant hormone receptor-positive (HR+) / human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Participants will be enrolled in two stages: a dose-escalation stage (Stage I) and an expansion stage (Stage II). Participants will be assigned to one of six regimens: GDC-0077 as a single agent (Arm A), GDC-0077 in combination with palbociclib and letrozole (Arm B), GDC-0077 in combination with letrozole (Arm C), GDC-0077 in combination with fulvestrant (Arm D), GDC-0077 in combination with palbociclib and fulvestrant (Arm E), and GDC-0077 in combination with palbociclib, fulvestrant, and metformin (Arm F).

Eligibility Criteria

Inclusion Criteria

  • Evaluable or measurable disease per RECIST, Version 1.1 (measurable disease only for Arm D)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of greater than or equal to (≥) 12 weeks
  • Adequate hematologic and organ function, including blood counts, liver and kidney function Stage I Arm A (GDC-0077):
  • Locally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor malignancy, including breast cancer Stages I and II, Arms B and C:
  • Postmenopausal female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer Stage II, Arms D, E, or F:
  • Female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer Stage II Arms D:
  • Prior treatment with CDK4/6 inhibitor Stages I and II:
  • All participants must provide tumor tissue from the primary or metastatic tumor site obtained from a prior or new biopsy or surgical procedure for detection of PIK3CA mutation by central laboratory test.

Exclusion Criteria

  • Inflammatory or metaplastic breast cancer
  • History of leptomeningeal disease
  • Type 1 or 2 diabetes requiring anti-hyperglycemic medication
  • Inability or unwillingness to swallow pills
  • Malabsorption syndrome or other condition that would interfere with enteral absorption
  • Known and untreated, or active central nervous system metastases
  • Uncontrolled pleural effusion or ascites
  • History of other malignancy within 5 years, except for treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
  • History of or active ventricular dysrhythmias or congestive heart failure requiring medication or symptomatic coronary heart disease
  • Congenital long QT syndrome, prolonged QT interval, or family history of sudden unexplained death or long QT syndrome Stage II:
  • Stage II Arms B, C, D, and E only: Prior treatment with >1 chemotherapy regimen for metastatic disease
  • Prior treatment with PI3K inhibitor
  • History of significant toxicity related to mTOR inhibitor requiring treatment discontinuation
  • Stage II Arms B and E only: prior CDK4/6 inhibitor treatment

Locations & Contacts

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Genentech Inc.

Trial IDs

Primary ID GO39374
Secondary IDs NCI-2017-00262, 2016-003022-17
Clinicaltrials.gov ID NCT03006172