LBA30 - Phase III ATALANTE/ov29 trial: Atezolizumab (Atz) versus placebo with platinum-based chemotherapy (Cx) plus bevacizumab (bev) in patients (pts) with platinum-sensitive relapse (PSR) of epithelial ovarian cancer (OC)

Background

Standard Cx for PSROC (> 6 months after last platinum dose) includes carboplatin plus pegylated liposomal doxorubicin (CbD) or gemcitabine (CbG) or paclitaxel (CbP) with or without bev. ATALANTE/ENGOT-ov29 (NCT02891824) is the first Phase III trial to evaluate Atz with Cx and bev for pts with PSROC.

Methods

Eligible pts had PSROC and ≤2 prior lines of Cx. Pts were randomised 2:1 to Atz (1200 mg, d1, q3w or 800 mg, d1&15, q4w with CbD up to 24 months [m]) or placebo (Pbo) with Cx at investigator-choice (CbD/CbG/CbP, 6 cycles) plus bev (15 mg/kg, d1, q3w or 10 mg/kg, d1&15, q4w), stratified by platinum-free interval, PD-L1 status on biopsy at study entry and Cx cohort. The co-primary endpoints are investigator-assessed progression-free survival (PFS) in the intent-to-treat (ITT) and PD-L1-positive (≥1% IC per tumour area) pts. Type I error was set at 0.025.

Results

From 10/2016 to 09/2019, 614 pts were randomized to Atz (n=410) or Pbo (n=204). Pts characteristics were balanced; Cx: CbD (63%), CbG (29%), CbP (8%), 1 (74%) or 2 (26%) prior lines, prior bev (62%). PD-L1 status was positive, negative, unknown in 38%, 49% and 13% of pts. Median follow-up was 36 m. The median PFS in the ITT pts was 13.5 and 11.2 m for the Atz and Pbo arms (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99; P = .041), and 15.2 vs 13.1 m in the PD-L1-positive pts (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30). At 333/491 planned events in the ITT pts, the median overall survival (OS) in the Atz and Pbo arms was 35.4 vs 30.6 m (HR, 0.81; 95% CI, 0.65 to 1.01). Grade ≥3 AEs and immune AEs were reported in 88% vs 86% and in 13% vs 8% of Atz and pbo pts respectively. There were five treatment related AEs of death (Atz, n=3; pbo, n=2). There was no significant difference in global health-related quality of life scores.

Conclusions

The ATALANTE trial evaluating the addition of Atz to standard therapy of PSROC pts did not meet its PFS co-primary endpoints in the ITT and PD-L1-positive pts. Encouraging OS data warrant further analyses with longer follow-up. Further research on ATALANTE biopsy samples is warranted to better decipher the immunological landscape of PSROC.

Clinical trial identification

2015-005471-24.

Editorial acknowledgement

Jennifer Kelly, Medi-Kelsey Limited.

Legal entity responsible for the study

ARCAGY-GINECO.

Funding

F. Hoffmann - La Roche Ltd.

Disclosure

J.E. Kurtz: Financial Interests, Personal, Advisory Board: Tesaro, Merck Serono, Clovis, AstraZeneca, GSK; Financial Interests, Personal, Other, Travel expenditure: AstraZeneca, PharmaMar, Roche, GSK; Financial Interests, Personal, Invited Speaker: Astra Zeneca, GSK, Bristol Myers Squib; Non-Financial Interests, Principal Investigator: Roche; Other, Immediate member family employed by Merck Sharp Dohme: Merck Sharp Dohme. E. Pujade-Lauraine: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, GSK; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, GSK; Financial Interests, Personal, Writing Engagements: Astra Zeneca, GSK; Financial Interests, Personal, Other, IDMC: INCYTE; Non-Financial Interests, Institutional, Full or part-time Employment: ARCAGY-GINECO; Non-Financial Interests, Institutional, Other, CEO: ARCAGY-Research. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Sotio, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019); Financial Interests, Institutional, Research Grant, Contracted Research ( via KU Leuven): Oncoinvent AS (2019-2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020). M.J. Rodrigues: Financial Interests, Personal, Invited Speaker: ASTRA ZENECA, GlaxoSmithKline, Merck Sharp and Dohme, Immunocore; Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibb, Merck Sharp and Dohme, Daiichi Sankyo; Non-Financial Interests, Invited Speaker: Société Française du Cancer. N. de Gregorio: Financial Interests, Personal, Other, Travel expenses: ASTRA ZENECA; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Myriad, GSK, MSD, Clovis, PharmaMar; Non-Financial Interests, Other: AGO Study group, Organkommission Ovar. J. Martinez-Garcia: Financial Interests, Personal, Advisory Board: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar; Financial Interests, Personal, Invited Speaker: Clovis Oncology, GSK-Tesaro, PharmaMar; Financial Interests, Personal, Other, Travel/accommodation/expenses for meeting: GSK-Tesaro, PharmaMar. 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, Expert Testimony, 2022: MSD. M.A. Mouret Reynier: Financial Interests, Personal, Other, Board participations and symposiums: Pfizer, Roche, Myriad, Astra-Zeneca, MSD, Lilly, Novartis, Eisai; Financial Interests, Institutional, Other, Clinical Trials: BMS, AbbVie, Roche, Novartis, MSD, Astra-Zeneca. F. Selle: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK-Tesaro, MSD, Sandoz (Novartis), Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Roche, GSK-Tesaro, ASTRA ZENECA, Immunogen, MSD, Incyte, Agenus. F. Joly Lobbedez: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, MSD, Janssen, ipsen, BMS, Bayer, Esai; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, MSD, Janssen, Ipsen, Amgen, Astellas; Financial Interests, Institutional, Invited Speaker: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Other, Other, travel: MSD, GSK. E. Bultot Boissier: Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Other, ESMO Member: ESMO. A. Floquet: Financial Interests, Personal, Other, Consultancy: GSK; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Clovis Oncology; Financial Interests, Invited Speaker, French coordinator - DUO Trial: AstraZeneca; Financial Interests, Invited Speaker, French coordinator- MIRASOL Trial: Immunogen. P. Heudel: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Seagen; Non-Financial Interests, Institutional, Principal Investigator, Coordinating PI: AstraZeneca. F. Heitz: Financial Interests, Personal, Invited Speaker: Amedes, Clovis; Financial Interests, Personal, Advisory Board: AstraZeneca, NovoCure, PharmaMar, Roche; Financial Interests, Institutional, Other, Trial Chair: Newoncology. All other authors have declared no conflicts of interest.