751P - Safety and tolerability of durvalumab (D) + carboplatin/paclitaxel (CP) + bevacizumab (B) followed by D, B + olaparib (O) maintenance (mtx) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) without a tumour BRCA1/BRCA2 mutation (non-tBRCAm) in the phase III DUO-O trial

Background

DUO-O, a double-blind, placebo (pbo)-controlled study, showed statistically significant and clinically meaningful PFS benefit at the primary analysis (data cutoff [DCO] 1) with the addition of D to CP + B followed by D + B + O mtx vs CP + B followed by B (Harter JCO 2023;41:17;LBA5506). We further characterize the safety and tolerability of the DUO-O regimen at DCO2 (18 Sep 2023).

Methods

Pts had high-grade epithelial AOC and primary, or planned interval, debulking surgery. Pts with non-tBRCAm AOC were randomized 1:1:1 after 1 cycle of CP ± B to Arm 1 (control): CP + B (up to 6 cycles) followed by B (total 15 mo); Arm 2: D + CP + B followed by D (total 24 mo) + B; or Arm 3: D + CP + B followed by D + B + O mtx (total 24 mo).

Results

The safety analysis set included 1127/1130 randomized pts (1127 received D/pbo; 990 received O/pbo). At DCO2, in Arms 1, 2 and 3, respectively, total median treatment (tx) duration was 14.7, 14.4 and 15.2 mo with B; 16.4, 13.8 and 17.6 mo with D/pbo; and 15.2, 14.7 and 15.9 mo with O/pbo mtx (noting the fixed tx durations); median no. of CP cycles was 6 for all arms. Overall, 62%, 66% and 72% of pts in Arms 1, 2 and 3, respectively, had grade ≥3 AEs; 22%, 26% and 35% had AEs leading to discontinuation of any tx, including 15%, 17% and 27% during the mtx phase. Anaemia (5%) was the most common AE leading to discontinuation in Arm 3. The rate of immune-mediated AEs was similar in Arms 2 and 3 (most were low grade; none were fatal). Grade ≥3 pure red cell aplasia (PRCA) and autoimmune haemolytic anaemia (AIHA) were reported in 3 pts in Arm 3 only (1 pt had PRCA, 1 had AIHA, 1 had both AEs); all events recovered/resolved. Additional AE summaries will be shown for the mtx phase.

Conclusions

In DUO-O, adding D to CP + B followed by D + B or D + B + O mtx had a manageable safety profile generally consistent with the known safety profiles of the individual agents.
^†Deceased, June 2024.

Table: 751P

Data cutoff (DCO) 2: 18 Sep 2023.

∗Including death;

†Top two AEs in Arm 3;

‡Grouped term;

§Programmatically derived AE, adverse event; CTCAE, Common Terminology Criteria for AEs (version 5.0).

Clinical trial identification

NCT03737643, 09/11/2018.

Editorial acknowledgement

Medical writing assistance was provided by Abbie Newman, BSc, at Cence, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

C. Aghajanian: Financial Interests, Institutional, Funding, Clinical trial funding. MSK PI, GOG3005: AbbVie; Financial Interests, Institutional, Funding, Clinical trial funding. International Coordinating Investigator & MSK PI, ARTIST: Artios Pharma; Financial Interests, Institutional, Funding, Clinical trial funding. MSK PI, SOLO1/GOG 3004; National Coordinating Investigator & MSK PI, D081RC00001; ENGOT-ov46; AGO-OVAR 23; GOG-3025: AstraZeneca; Financial Interests, Institutional, Funding, Clinical trial funding. MSK PI, ARIEL 2 & 3: Clovis; Financial Interests, Institutional, Funding, Clinical trial funding. MSK PI, GOG3015 (IMagyn050): Genentech/Roche; Non-Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board. Virtual Advisory Board 6/30/21 (no consulting fee or honorarium): Blueprint Medicine; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board. Global Cervical and Ovarian Cancer Virtual Advisory Board 7/10/23 (honorarium): Merck; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board. AZ eVOLVE DMC 4/26/23-ongoing (consulting fee) AND Future Clinical Strategies for Endometrial Cancer Virtual Advisory Board 3/13/24 (honorarium): AstraZeneca; Non-Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board. RAMP 301 Steering Committee, 3/6/24-ongoing (no consulting fee or honorarium): Verastem; Non-Financial Interests, Personal, Member of Board of Directors: GOG Foundation, NRG Oncology. B. Schmalfeldt: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD, Eisai, Daiichi Sankyo, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, MSD, Eisai, Daiichi Sankyo, Roche; Financial Interests, Institutional, Research Funding: AstraZeneca, GSK, MSD, Eisai, Roche; Non-Financial Interests, Personal, Member of Board of Directors: DGGG. J. Kim: Financial Interests, Personal, Advisory Board: Takeda Korea, GSK Korea, Boryung, Vifor Pharma, MSD Korea, LG Pharma; Financial Interests, Personal, Invited Speaker: CMIC, AstraZeneca, Janssen. G. Marquina Ospina: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, GSK/Tesaro, Clovis Oncology, Bayer, EISAI, Lilly, Medicamenta, PharmaMar, Ipsen, MSD, Grünenthal, Kyowa Kirin, Teva, Otsuka; Financial Interests, Personal, Advisory Board: GSK/Tesaro, Pfizer, PharmaMar, Lilly, Clovis Oncology, Boehringer Ingelheim, Deciphera, Eisai, Otsuka; Other, Transport, hotel accommodation and registration for ESGO 2024: AstraZeneca; Other, Transport, hotel accommodation and registration for ESMO 2024: Lilly; Other, Registration for ASCO 2023: MSD; Other, Transport, hotel accomodation and registration for GSK Masterclass on endometrial cancer 2024: GSK. V. Salutari: Financial Interests, Personal, Advisory Board: Astazeneca, Eisai; Financial Interests, Personal, Invited Speaker: MSD, GSK; Financial Interests, Institutional, Local PI: MSD, AstraZeneca; Financial Interests, Personal and Institutional, Steering Committee Member: MSD. C. Lebreton: Financial Interests, Personal, Expert Testimony: Clovis Oncology, Eisai, GSK, MSD; Financial Interests, Personal, Advisory Board: GSK. S. Lheureux: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, GSK, Shattuck Labs, Novartis, Roche/Genentech; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck, GSK, Shattuck Labs, Roche/Genentech; Financial Interests, Institutional, Research Funding: Tesaro, AstraZeneca, Roche/Genentech, Regeneron, Merck, GSK, Repare Therapeutics. A. Burges: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Tesano; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Roche, Tesano. R.M. Wenham: Financial Interests, Personal and Institutional, Research Funding: GSK/Tesaro, Eisai, AstraZeneca, Merck, Genentech, Seagen, Sonnett Biotherapeutics, Tapimmune, Mersana, Regeneron, OnTarget Labs, Ovation Diagnostics; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: GSK/Tesaro, Eisai, AstraZeneca, Merck, Genentech, Seagen, Sonnett Biotherapeutics, Tapimmune, Mersana, Regeneron, OnTarget Labs, Ovation Diagnostics; Financial Interests, Personal, Speaker, Consultant, Advisor: Curioscience, OncLive, Shattuck Labs, Clovis, Legend Biotech; Financial Interests, Personal, Research Funding: Clovis; Financial Interests, Institutional, Research Funding: Anixa Biosciences. L. Marshall: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Institutional, Stocks or ownership: AstraZeneca. P. Harter: Financial Interests, Personal, Advisory Board, Value includes honoraria for lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, includes honoraria for lectures: GSK, Roche, MSD; Financial Interests, Personal, Invited Speaker: Amgen, Stryker, Zailab, Eisai, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Clovis, ImmunoGen, Novartis, Mersana, Miltenyi, Exscientia; Financial Interests, Personal, Other, IDMC member: Sotio; Financial Interests, Institutional, Trial Chair: AstraZeneca, Roche, GSK, ImmunoGen; Financial Interests, Institutional, Local PI: Genmab; Financial Interests, Institutional, Funding: Seagen, Clovis; Financial Interests, Institutional, Other, Co-investigator: Novartis; Non-Financial Interests, Principal Investigator: AstraZeneca; Other, Travel support for conference: AstraZeneca. All other authors have declared no conflicts of interest.