Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer

Trial ID #	NCT01623349
Phase	I
Drug Class	Signaling Pathway Inhibitors: PI3K-AKT-mTOR/pan-PI3K
Drug Name	Buparlisib
Alternate Drug Names	BKM120, NVP-BKM120, AN2025
Drugs in Trial	Buparlisib, Olaparib
Eligible Participant	Advanced solid tumors
Patients Enrolled	118 (46 ovarian)
Therapy Setting	Recurrence
Study Design	Open-Label, Non-randomized
Endpoints	ORR, DCR, RP2D, evaluated per RECIST
Biomarkers	Exploratory: gBRCA1/2
Efficacy	Ola+Bup: RP2D: Bup 50 mg qd and Ola 300 mg bid ORR: 29% (12PR, n=41) DCR: 78% (12PR, 20SD, n=41) Exploratory analysis Pt status, gBRCA status: Pt-S: ORR: 32% (6PR, n=19) Pt-R: ORR: 27% (6PR, n=22) gBRCA WT: ORR: 13% (1PR, n=8) gBRCA MUT: ORR: 29% (8PR, n=28)
Clinically Significant Adverse Events	Dose Limiting Toxicities: depression (n=1), transaminitis (n=2), hyperglycemia (n=1) Serious AE: none Grade 3-4 AE: none 36% and 28% of patients experienced low grade depression or anxiety, respectively
Conclusion	Drug combination with serious CNS side effects
Reference	Matulonis U et al. Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high grade serous ovarian and breast cancer. Ann Oncol (2017) 28: 512-518 https://www.ncbi.nlm.nih.gov/pubmed/27993796