Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected

EPIK-O: A Phase III, Multi-center, Randomized (1:1), Open-label, Active-controlled, Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Olaparib as Compared to Single Agent Cytotoxic Chemotherapy, in Participants With no Germline BRCA Mutation Detected, Platinum-resistant or Refractory, High-grade Serous Ovarian Cancer

The objective of this study was to assess the efficacy and safety of the combination of alpelisib and olaparib compared with single agent cytotoxic chemotherapy in patients with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected.

This study included adult women with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected. Participants were randomized in a 1:1 ratio to either alpelisib plus olaparib or single agent cytotoxic chemotherapy (paclitaxel or PLD) in this open-label, active controlled study.

Participants continued to receive study treatment until disease progression, unacceptable toxicity that precludes further treatment, or until discontinuation of study treatment due to any other reason. After treatment discontinuation, all participants entered in the post-treatment follow-up period, which consisted of a safety follow-up visit and a 9-week post-progression visit. Once they completed the post-treatment follow-up, participants then entered the survival follow-up period.

Key Inclusion Criteria:

• Participant has histologically confirmed diagnosis of high-grade serous or high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
• Measurable disease, i.e., at least one measurable lesion per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation)
• If no measurable disease is present, the disease should be assessable by Gynecologic Cancer Intergroup criteria (GCIC) for CA-125
• Participant has no germline BRCA1/2 mutation as determined by an FDA-approved assay
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participant has platinum-resistant (progression within one to six months after completing platinum-based therapy) or platinum refractory disease (progression during treatment or within 4 weeks after the last dose), where platinum-based therapy is not an option, according to the GCIG 5th Ovarian Cancer Consensus Conference definitions (Wilson et al 2016). The platinum-based chemotherapy regimen does not necessarily need to be the last regimen the participant received prior to study entry
• Participant must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment
• Participant has received prior bevacizumab or is not eligible to receive bevacizumab due to medical reasons.

Key Exclusion Criteria:

• Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor
• Participant is concurrently using other anti-cancer therapy
• Participant is in a state of small or large bowel obstruction or has other impairment of gastrointestinal (GI) function or GI disease
• Participant has had surgery within 14 days prior to starting study drug or has not recovered from major adverse effects
• Participant has not recovered from all toxicities related to prior anticancer therapies to baseline or NCI CTCAE Version 4.03 Grade ≤1. Exception to this criterion: participants with any grade of alopecia are allowed to enter the study
• Participant has an established diagnosis of diabetes mellitus type I or uncontrolled type II based on fasting plasma glucose and HbA1c
• Participants with liver impairment and Child Pugh score B or C
• Participant has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to randomization, and who has not recovered to baseline, grade 1 or better from related adverse effects of such therapy (with the exception of alopecia)
• Participant has a known hypersensitivity to any of the study drugs or excipients
• Participant has a history of myelodysplastic syndrome or acute myeloid leukemia, or presents clinical and/ or laboratory features suggestive thereof.

Other inclusion/exclusion criteria may apply