Phase Ib Dose-escalation Trial of Taselisib (GDC-0032) in Combination With Anti-HER2 Therapies in Participants With Advanced HER2+ Breast Cancer
This research study is a way of gaining new knowledge about the combination of Taselisib with other drugs in the treatment of metastatic breast cancer. Taselisib is an investigational drug which works by blocking a protein called PI3K (phosphoinositide 3-kinase) that helps cancer cells grow. This drug has been used in laboratory experiments and information from these studies suggests that this drug may help to prevent or slow the growth of cancer cells. The main purpose of this study is to find the appropriate dose of Taselisib to be used with other drugs in further clinical studies. This is an open-label, 3+3 dose-escalation phase Ib study to identify the Maximum Tolerated Dose(s) (MTD) and to identify the recommended phase 2 dose (RP2D) of Taselisib. This study will be conducted in 4 separate arms. (A-D).
• Metastatic, locally advanced , or locally recurrent breast cancer
• Histologically confirmed HER2+ invasive breast cancer
• Measurable or non-measurable disease per RECIST v1.1
• Prior therapy - Prior trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1) are allowed. Patients who have received prior therapy with Taselisib (GDC-0032) or BYL-719 are excluded. There is no limit on the number of prior lines of therapy.
• ECOG performance status 0 or 1
• Normal organ and marrow function as defined below:
‣ Absolute neutrophil count ≥ 1,500/mm3
⁃ Platelets ≥100,000/mm3
⁃ Total bilirubin \< 1.5 X institutional upper limit of normal. For patients with Gilbert syndrome, the direct bilirubin should be within the institutional normal range
⁃ AST (SGOT) and ALT (SGPT) \< 2.5 X institutional upper limit of normal
⁃ Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min
⁃ Fasting glucose ≤ 120 mg/dL and HbA1c \< 7%
• Left ventricular ejection fraction ≥ 50%
• Women of childbearing potential (including those who have had a tubal ligation) must have a documented negative pregnancy test within 14 days prior to planned initiation of Taselisib.
• Ability to understand and the willingness to sign a written informed consent document.
• For Part 2: patients must have tissue that is amenable to biopsy and must be willing to undergo research biopsy. Patients who undergo an attempted research biopsy procedure for the purpose of this protocol, and in whom inadequate tissue is obtained, are not required to undergo a repeat biopsy in order to continue on protocol.