Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: 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

Summary: 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: 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

Relevance to patient case: possibly relevant