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

Advanced solid tumors (OvCa: HGS or gBRCA MUT of any histology)

118 [28 ovarian; 21 HGS, 5 poorly differentiated adenocarcinoma NOS, 1 carcinosarcoma, 1 mixed HGS and transitional cell carcinoma; median 3 prior therapies (2-5)]

Recurrence

Open-Label, Non-randomized

ORR, DCR, DoR, PFS, OS, RP2D, evaluated per RECIST

Exploratory: gBRCA1/2

RP2D: Alp 200 mg qd and Ola 200 mg bid
ORR: 36% (10PR, n=28) (93% Pt-R/Pt-Rf)
ORR: 34.6% (9PR, n=26) (all Pt-R/Pt-Rf)
DCR: 86% (10PR, 14SD, n=28)
DoR: 5.5 months (0.5-13.2)
PFS: 7.2 months (4.9-9.0)
OS: 21.3 months (11.4-23.7)

Exploratory analysis BRCA status in Pt-R/Pt-Rf patients:
gBRCA WT: ORR: 31.3% (5PR, n=16)
gBRCA MUT: ORR: 33.3% (3PR, n=9)
BRCA WT: ORR: 33.3% (4PR, n=12)
BRCA MUT: ORR: 30.8% (4PR, n=13)

Dose Limiting Toxicities: hyperglycemia (n=2), rash (n=1), neutropenia and fever (n=1)
Serious AE: none
Grade 3-4 AE: hyperglycemia (16%)

Encouraging activity of alpelisib+olaparib combination in gBRCA WT patients

Konstantinopoulos PA et al. Olaparib and alpha-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. Lancet (2019) 20(4):570-580
https://www.ncbi.nlm.nih.gov/pubmed/30880072