747MO - First results from the ENGOT-GYN2/GOG-3051/BOUQUET phase II biomarker-directed platform study: Cobimetinib (cobi) or atezolizumab (atezo) + bevacizumab (bev) for persistent/recurrent rare epithelial ovarian cancer (eOC)

Background

BOUQUET (NCT04931342) is an ongoing platform study evaluating multiple treatments in biomarker-selected patients (pts) with rare eOC that tends to respond less well to standard therapies. We report interim results from the cobi (MEK1 inhibitor) and atezo (anti-PD-L1) + bev (anti-VEGF) arms.

Methods

Eligible pts had measurable persistent/recurrent platinum-resistant (not primary-refractory) non-high-grade serous/non-high-grade endometrioid eOC by central pathological assessment and had received 1–4 prior lines of non-hormonal systemic therapy. Tumour samples were tested centrally using the FoundationOne CDx NGS assay. Pts with BRAF/KRAS/NRAS or NF1 alterations were treated with oral cobi 60 mg/d, d1–21 q28d. Pts ineligible for any open biomarker-selected arm received IV atezo 1200 mg + bev 15 mg/kg both on d1 q21d. The primary efficacy endpoint is investigator-assessed confirmed objective response rate (cORR) per RECIST v1.1.

Results

As of the clinical cut-off date, 20 pts have received cobi (8 low-grade serous ovarian cancer [LGSOC], 5 mucinous carcinoma [MUC], 5 clear-cell carcinoma [CCC], 1 carcinosarcoma [CS], 1 mesonephric-like adenocarcinoma [MLA]) and 21 atezo + bev (15 LGSOC, 3 CCC, 2 MUC, 1 CS). Pts were heavily pretreated (≥3 prior lines: 65% of cobi pts, 48% of atezo + bev pts). cORRs were 16% with cobi and 14% with atezo + bev (Table). For cobi-treated LGSOC + MLA, cORR was 33% (3/9) and disease control rate (complete/partial response [CR/PR] or stable disease ≥16 wks) was 89% (8/9). At data cut-off, treatment was ongoing in 9 pts in the cobi arm and 15 in the atezo + bev arm; all CR/PR in both arms were ongoing.

Table: 747MO

^an=19 for efficacy (no measurable disease at baseline in 1 pt). ^bCardiac arrest, not considered treatment related.

Conclusions

The 33% cORR with cobi in heavily pretreated LGSOC/MLA is promising; additional pts will be enrolled. Tolerability was consistent with prior experience. BOUQUET continues to evaluate biomarker-driven therapies for rare eOC.

Clinical trial identification

NCT04931342.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd.).

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Eisai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. S. Pignata: Financial Interests, Personal, Advisory Board: Roche, AZ, MSD, Clovis, GSK, PharmaMar; Financial Interests, Institutional, Funding: Roche, MSD, Pfizer, AZ. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: BeiGene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. R.L. Coleman: Financial Interests, Personal, Advisory Board: AstraZeneca, Agenus, Alkermes, Immunogen, Roche/Genentech, GSK, Genmab/Seagen, Epsilogen, Myriad Genetics; Financial Interests, Personal, Invited Speaker: AstraZeneca, Genmab/Seagen; Non-Financial Interests, Principal Investigator: AbbVie, immunogen, Roche/Genentech, Merck, Genmab, clovis; Non-Financial Interests, Project Lead, MyLung Consortium: US Oncology Research. J. Brown: Financial Interests, Personal, Speaker’s Bureau, Former member: Eisai; Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Clovis, Genentech, Verastem, Caris; Financial Interests, Institutional, Research Funding: Genentech, GSK/Tesaro. 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. F. Selle: Financial Interests, Personal, Speaker, Consultant, Advisor, Also travel/accommodation/expenses: AstraZeneca, GSK/Tesaro, MSD; Financial Interests, Personal, Financially compensated role: Sandoz (Novartis), Clovis Oncology; Financial Interests, Institutional, Research Funding: Roche, GSK/Tesaro, AstraZeneca, Immunogen, MSD, Incyte, Agenus; Financial Interests, Personal, Other, Also travel/accommodation/expenses: Roche. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020 : Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021 : AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Advisory Board, 2022: MSD; Financial Interests, Personal and Institutional, Research Grant: PharmaMar; Financial Interests, Research Grant: ONXEO. C. Gourley: Financial Interests, Personal, Invited Speaker, Both personal and institutional: Roche, AstraZeneca, MSD, GSK, Clovis, Chugai, Takeda, Eisai; Financial Interests, Personal, Advisory Board, Both personal and institutional: AstraZeneca, MSD, GSK; Financial Interests, Personal, Writing Engagement: Cor2Ed, PeerVoice; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Aprea, Nucana, Medannex; Financial Interests, Institutional, Local PI: GSK, BerGenBio, MSD, Clovis, Roche, Verastem; Non-Financial Interests, Other, Committee member: Cancer Research UK Clinical Research Committee; Non-Financial Interests, Other, Committee Member: German Cancer Aid Scientific Review Committee, International Clinical Cancer Research Committee, Institut National du Cancer, France. G. Richardson: Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb, Roche, Genentech, Shanghai Fosun Pharmaceutical Development Company; Financial Interests, Institutional, Local PI: AstraZenica, Merck, Takeda, BeiGene, Pfizer, CBT Pharmaceuticals, Corvus Pharmaceuticals, Novotech, Shanghai Henlius Biotech Inc, Five Prime Therapeutics Inc., Suzhou Alphamab Co, Boehringer Ingelheim, Adagene Inc., Bio-Thera Solutions, ChemoCentryx, Curon Biopharmaceutical, D3io Co Ltd., Inventis Bio, Senz Oncology Pty Ltd., Genfleet Therapeutics, GeneQuantum Healthcare Co Ltd., Keythera Pharmaceuticals Pty Ltd., LaNova Australia Pty Ltd., Medicenna Therapeutics Inc., Minghui Pharmaceutical, Neoleukin Therapeutics, PharmAbcine Australia Pty Ltd., Remegen, Seattle Genetics, Surface Oncology, Eucure Biopharma, Janssen Oncology, ImmunGen Inc., Imugene Ltd., Therapim, Agenus. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, SOTIO, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. L. Yauch: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. M. Dieterich: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. V. Krishnan: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. O. Calas-Zeroug: Financial Interests, Institutional, Other, Cytel (my employer) is contracted as clinical research organisation for this and other Roche trials: F. Hoffmann-La Roche. 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; Financial Interests, Personal, Advisory Board: Clovis, Immunogen, Novartis, Mersana, Miltenyi; 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; Non-Financial Interests, Principal Investigator: AstraZeneca. All other authors have declared no conflicts of interest.