A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BKM120 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors

Trial ID #	NCT01363232
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	Binimetinib, Buparlisib
Eligible Participant	Advanced solid tumors with RAS or RAF alterations
Patients Enrolled	89, median 3 prior therapies (1-12); 19 ovarian
Therapy Setting	Recurrence
Study Design	Open-Label, Non-randomized
Endpoints	ORR, DCR, PFS, RP2D, evaluated per RECIST
Biomarkers	KRAS, NRAS, BRAF alterations
Efficacy	RP2D: 80 mg buparlisib qd+45 mg binimetinib bid ovarian patients at RP2D: ORR: 27.8% (5PR, n=18; 2 KRAS MUT, 1 NRAS MUT, 2 BRAF MUT) DCR: 61.1% (5PR, 6SD, n=18) PFS: 3.7 months
Clinically Significant Adverse Events	Serious AE: Grade 3-4 AE: maculopapular rash (12.4%)
Conclusion	Buparlisib+binimetinib shows encouraging efficacy in RAS/RAF MUT ovarian cancer patients, but with significant toxicity
Reference	Bardia A et al. Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. Oncologist (2020) 25(1):e160-e169 https://www.ncbi.nlm.nih.gov/pubmed/31395751