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 DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Olaparib
Alternate Drug Names AZD2281, Lynparza
Drugs in Trial Alpelisib, Olaparib
Eligible Participant

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

Patients Enrolled

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)]

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

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

Biomarkers

Exploratory: gBRCA1/2

Efficacy

RP2D: Alp 200 mg qd and Ola 200 mg bid
ORR: 36% (10PR, n=28) (93% Pt-R)
DCR: 86% (10PR, 14SD, n=28)
DoR: 5.6 months (0.5-13.2)
PFS: 7.2 months (4.9-9.0)
OS: 21.3 months (11.4-23.7)

Exploratory analysis gBRCA status in Pt-R/Pt-Rf patients:
gBRCA WT: ORR: 35% (6PR, n=17)
gBRCA MUT: ORR: 3PR, n=10

Clinically Significant Adverse Events

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

Conclusion

Encouraging activity of alpelisib+olaparib combination in gBRCA WT patients

Reference

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)
https://www.ncbi.nlm.nih.gov/pubmed/30880072