Abstract 733P
Background
In high-grade AOC patients, the combination of immunotherapy, PARP inhibitors (PARPi), and antiangiogenic agents, may enhance the efficacy of each treatment. Different chemotherapy-free combinations were previously found to be feasible. A significant activity of the Durva + Ola +/- Bev combination was reported in platinum-sensitive recurrent (PSR) AOC in the MEDIOLA trial. However the efficacy of the triplet in platinum resistant relapse (PRR) has never been assessed.
Methods
We performed an open-label, multicentre single-arm phase II trial assessing the efficacy and toxicity of the durvalumab 1120 mg q3w + bevacizumab 15 mg/kg q3w + olaparib 300 mg bid combination, in pts with high-grade epithelial AOC with PRR and PSR, regardless of the number of previous lines of therapy. Previous Bev or PARP inhibitor was allowed. Treatment was given until progression or severe toxicity. Disease-control rate (DCR) at 3 months (PRR) and 6 months (PSR) was the principal endpoint.
Results
From March 1st, 2019 to January 29th, 2020, 74 patients with high-grade AOC pts were included, 41 of whom had PRR. Table: 733P
| PRR cohort (N=41) | PSR cohort (N=33) | |
| Median age | 66 [38 – 89] | 65 [49 – 81] |
| High grade serous carcinoma | 38 (93%) | 33 (100 %) |
| BRCA 1/2 mutation | 4 (10 %) | 11 (33 %) |
| Previous bevacizumab | 35 (85 %) | 21 (64 %) |
| Previous PARPi | 13 (32 %) | 17 (52 %) |
| Nb of previous lines of chemotherapy (median) | 3 [1 – 8] | 2 [1 – 8] |
With a 15.5 month median follow-up, DCR was 70 % [90% CI : 56 – 80] at 3 months in the PRR cohort (H0 rejected) and 44 % [29 – 57] at 6 months in the PSR cohort (H0 not rejected). Median PFS in PRR and PSR pts were 4.1 [3.5 – 5.9] and 4.9 [2.9 – 7] months, respectively. Median OS were 18.8 [9.6 – NR] and 18.5 [15.6 – NR] months. In the PRR cohort, 6-months DCR was 30 % and 7 pts (17 %) are still under treatment ≥ 20 months after inclusion. Neither toxic death nor major safety signal was observed. Eleven pts definitely stopped Ola, 8 pts stopped Bev and 6 Durva for toxicity, respectively.
Conclusions
The chemo-free combination of Durva, Ola and Bev was safe and effective in both cohorts. In heavily pre-treated pts with PRR, OS was longer than usually reported with chemotherapy. The BOLD combination warrants further investigation in this setting.
Clinical trial identification
NCT04015739.
Editorial acknowledgement
Legal entity responsible for the study
ARCAGY-GINECO.
Funding
ARCAGY-GINECO & AstraZeneca.
Disclosure
G. Freyer: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: biogaran; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: BMS; Non-Financial Interests, Principal Investigator: Novartis. A. Floquet: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Clovis Oncology; Other, Personal, Other, Financial help for congress: AstraZeneca; Other, Personal, Other, Financial help for congress: GSK; Other, Personal, Other, Financial help for congress: MSD; Other, Personal, Other, Financial help for congress: Pharma Mar; Other, Personal, Other, Financial help for congress: Roche. O. Tredan: Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: MSD-Merck; Financial Interests, Personal, Other, personal fees: AstraZeneca; Financial Interests, Personal, Other, personal fees: Novartis-Sandoz; Financial Interests, Personal, Other, personal fees: Pfizer; Financial Interests, Personal, Other, personal fees: Lilly; Financial Interests, Personal, Other, personal fees: Seagen; Financial Interests, Personal, Other, personal fees: Daiichi Sankyo; Financial Interests, Personal, Other, personal fees: Eisai; Financial Interests, Personal, Other, personal fees: Pierre Fabre; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: MSD-Merck; Financial Interests, Personal, Research Grant: BMS. F. Selle: Financial Interests, Personal and Institutional, Other: AstraZeneca; Financial Interests, Personal and Institutional, Other: GSK-Tesaro; Financial Interests, Personal and Institutional, Other: MSD; Financial Interests, Personal, Other: Sandoz (Novartis); Financial Interests, Personal, Other: Clovis oncology; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Immunogen; Financial Interests, Institutional, Other: Incyte; Financial Interests, Institutional, Other: Agenus. C. Abdeddaim: Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Principal Investigator, financial interest: Debio Pharm; Financial Interests, Institutional, Other, coordinating PI: Epizyme; Financial Interests, Institutional, Principal Investigator, financial Interest: GSK; Financial Interests, Institutional, Principal Investigator, financial Interest: MSD. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK; Financial Interests, Personal, Invited Speaker, Educational: Medscape; Financial Interests, Personal, Invited Speaker, Educational: Onco+; Financial Interests, Institutional, Other, Steering Committee: MSD; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Clovis; Financial Interests, Institutional, Invited Speaker, Educational: Kephren; Financial Interests, Institutional, Advisory Board: Ability Ph; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Advisory Board: Tesaro; Financial Interests, Institutional, Invited Speaker: Tesaro; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Advisory Board: Merck Serono; Financial Interests, Institutional, Invited Speaker: Clovis; Financial Interests, Institutional, Advisory Board: Apmonia; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO; Financial Interests, Institutional, Research Grant, PI translational researcha: Sanofi; Financial Interests, Institutional, Research Grant, PI translational research: AstraZeneca; Financial Interests, Institutional, Funding, CI clinical trial: AstraZeneca; Financial Interests, Institutional, Research Grant, Int CI clinical trial: Ose Immunotherapeutics; Financial Interests, Institutional, Funding, PI clinical trial: Agenus; Financial Interests, Institutional, Funding, PI 5 clinical trial: Roche; Financial Interests, Institutional, Funding, PI clinical trial: BMS; Financial Interests, Institutional, Funding, PI 2 clinical trial: AstraZeneca; Financial Interests, Institutional, Funding, PI clinical trial: Lovance; Financial Interests, Institutional, Funding, PI 3 clinical trial: MSD; Financial Interests, Institutional, Funding, PI clinical trial: GSK; Non-Financial Interests, Institutional, Other, Academic research project: Owkin; Non-Financial Interests, Institutional, Other, Academic research project: LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer. M. Fabbro: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK. L. Gladieff: Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Clovis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Institutional, Advisory Board: MSD. C. Sajous: Financial Interests, Personal, Advisory Board, expert board consulting: Eisai. All other authors have declared no conflicts of interest.