814MO - Phase II study of olaparib (O) plus durvalumab (D) and bevacizumab (B) (MEDIOLA): Initial results in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum sensitive relapsed (PSR) ovarian cancer (OC)

Background

Olaparib is a PARP inhibitor approved in first-line and recurrent OC. Results of O+D in gBRCAm PSR OC have been presented. MEDIOLA (NCT02734004) then evaluated combining O+D (doublet cohort) or O+D+B (triplet cohort) in non-gBRCAm PSR OC. Here we present initial results.

Methods

Pts had confirmed non-gBRCAm PSR OC and had progressed after receiving 1–2 prior lines (L) of platinum-based chemotherapy. Pts received O 300 mg bid and D 1.5g IV q4 weeks (w) and B 10 mg/kg q2w (triplet only) until progressive disease. Tumours were assessed by RECIST v1.1 at baseline and q8w. Primary endpoints were safety and 24-w disease control rate (DCR). Secondary endpoints included objective response rate (ORR), median duration of response (mDOR) and progression-free survival (PFS).

Results

From Nov 2018 to Feb 2019, 32 pts (69% 2^nd L) enrolled and received O+D; from May 2018 to Jan 2019, 31 (68% 2^nd L) enrolled and received O+D+B. At the data cut-off 13 Feb 2020, 22% of O+D and 42% of O+D+B pts remained on treatment. The most common grade ≥3 AEs in O+D were anaemia, lipase increased and neutropenia and anaemia, hypertension, fatigue, lipase increased, and neutropenia in O+D+B. Two (6%) and five (16%) pts discontinued one or more study drug due to an AE in O+D and O+D+B, respectively. Efficacy is summarized in the table. Efficacy in biomarker subgroups, including by presence of genome-wide loss of heterozygosity, will be presented. Table: 814MO

CI, confidence interval; IQR, interquartile range.

Conclusions

Combining O+D and O+D+B was well tolerated in pts with non-gBRCAm PSR OC, consistent with the known safety profiles of the single agents. The DCR for the doublet cohort did not meet the prespecified target of 80%. The 95% CI for DCR in the triplet cohort included the prespecified target of 80%. ORR and PFS in the triplet cohort demonstrate promising activity in non-gBRCAm PSR OC, and in this group the ORR and PFS are higher than reported for single-agent PARP or VEGF inhibitors.

Clinical trial identification

NCT02734004.

Editorial acknowledgement

Medical writing assistance was provided by Elin Pyke, MChem, from Mudskipper Business, Ltd, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y. Drew: Honoraria (self), Honoraria (institution), Advisory/Consultancy: AstraZeneca. R.T. Penson: Honoraria (institution), Advisory/Consultancy: AstraZeneca. D.M. O'Malley: Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Clovis; Honoraria (self), Honoraria (institution): Tesaro & Immunogen; Honoraria (self): Ambry; Honoraria (self), Honoraria (institution): Janssen/J&J; Honoraria (self), Honoraria (institution): AbbVie; Honoraria (self), Honoraria (institution): Regeneron; Honoraria (self), Honoraria (institution): Amgen; Honoraria (self), Honoraria (institution): Novocure; Honoraria (self), Honoraria (institution): Genentech/Roche; Honoraria (institution): VentiRx; Honoraria (institution): Array Biopharma; Honoraria (institution): EMD Serono; Honoraria (institution): Ergomed; Honoraria (institution): Ajinmoto Inc; Honoraria (institution): Ludwig Cancer Research; Honoraria (institution): Stemcentrx, Inc.; Honoraria (institution): Cerulean Pharma; Honoraria (self), Honoraria (institution): GOG Foundation; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Serono Inc.; Honoraria (institution): Tracon Pharmaceuticals; Honoraria (institution): Yale University; Honoraria (institution): New Mexico Cancer Care Alliance; Honoraria (institution): INC Research, Inc.; Honoraria (institution): inVentiv Health Clinical; Honoraria (institution): Iovance Biotherapeutics, Inc.; Honoraria (institution): PRA International; Honoraria (self): Myriad Genetics, Tarveda; Honoraria (self), Honoraria (institution): Eisai, Agenus, GSK, Merck. S. Zimmermann: Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self), Non-remunerated activity/ies: Eli Lilly; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: MSD; Honoraria (self), Non-remunerated activity/ies: Novartis; Non-remunerated activity/ies: Amgen; Non-remunerated activity/ies: Astellas; Spouse/Financial dependant: Merck KGaA; Non-remunerated activity/ies: Vifor. P. Roxburgh: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (self): GlaxoSmithKline; Honoraria (institution): Tesaro. B. You: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca. S. Domchek: Honoraria (self): AstraZeneca; Honoraria (self): Clovis; Honoraria (self): Bristol-Myers Squibb. H. Gao: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. H. Angell: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. K. Meyer: Research grant/Funding (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. L. Opincar: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. L. Ottesen: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. D.O. Koralek: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. S. Banerjee: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. All other authors have declared no conflicts of interest.