LBA31 - Primary results from IMagyn050/GOG 3015/ENGOT-OV39, a double-blind placebo (pbo)-controlled randomised phase III trial of bevacizumab (bev)-containing therapy +/- atezolizumab (atezo) for newly diagnosed stage III/IV ovarian cancer (OC)

Background

Atezo, which targets PD-L1, is effective in several cancers. Blocking tumour-associated VEGF may promote T-cell infiltration into the tumour bed and boost anti-tumour immune response, justifying combination with bev. Dual VEGF-A and PD-L1 blockade is effective in lung and hepatocellular cancers.

Methods

IMagyn050 (NCT03038100) enrolled patients (pts) with newly diagnosed untreated stage III/IV OC who underwent either primary cytoreductive surgery (PCS) with gross residual disease or neoadjuvant chemotherapy (NACT) and interval surgery. Eligible pts were randomised 1:1 to atezo 1200 mg or pbo cycles 1–22, with paclitaxel 175 mg/m² + carboplatin AUC6 cycles 1–6 + bev 15 mg/kg cycles 2–22 (PCS pts), omitting peri-operative bev in NACT pts. Cycles were repeated q3w. Stratification factors were: stage (III vs IV), ECOG PS (0 vs 1/2), PD-L1 staining in immune cells (IC <1% vs ≥1% [PD-L1+]) and treatment strategy (PCS vs NACT). The co-primary endpoints were investigator-assessed progression-free survival (PFS; RECIST v1.1) and overall survival (OS) in the intent-to-treat (ITT) and PD-L1+ populations. PFS was tested in parallel in the two populations; OS was tested hierarchically.

Results

Of 1301 enrolled pts, ∼25% received NACT. At the data cut-off (30 Mar 2020) median follow-up was ∼20 months in both arms. There was no statistically significant PFS improvement in either the ITT population (HR 0.92 [95% CI 0.79–1.07]; median 18.4 months with pbo vs 19.5 months with atezo) or the PD-L1+ population (HR 0.80 [0.65–0.99], median 18.5 vs 20.8 months, respectively). Exploratory PFS analyses in the PD-L1 IC ≥5% subgroup showed a trend favouring atezo. Though immature, first interim OS results did not show significant benefit from atezo. Similar proportions discontinued any study treatment for AEs (22% pbo vs 26% atezo pts). The safety profile of atezo + bev + chemotherapy was consistent with expected AEs.

Conclusions

Atezo did not significantly improve PFS in the ITT or PD-L1+ population. The combination was generally well tolerated with manageable AEs. Exploratory biomarker subgroup analyses are ongoing.

Clinical trial identification

NCT03038100.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd), funded by F Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

K.N. Moore: Advisory/Consultancy: Aravive; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Clovis; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): GSK/Tesaro; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Immunogen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Mersana; Advisory/Consultancy: OncoMed/Mereo; Advisory/Consultancy: VBL Therapeutics; Advisory/Consultancy: Vavotar; Advisory/Consultancy: Tarveda; Research grant/Funding (institution): PTC Therapeutics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): OncoMed. M. Bookman: Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: AstraZeneca; Non-remunerated activity/ies, Steering Committee: Roche; Honoraria (self): AbbVie; Honoraria (self): Aravive; Honoraria (self): Mateon; Honoraria (self): Immunogen. J. Sehouli: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): PharmaMar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: GSK/Tesaro; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novocure; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Leadership role: NOGGO; Leadership role: ESGO; Leadership role: PARSGO; Leadership role: AGO; Research grant/Funding (institution): Roche Diagnostics; Research grant/Funding (institution): Medac. G. Scambia: Advisory/Consultancy: Tesaro Bio Italy S.r.l/GlaxoSmithKline; Advisory/Consultancy: Johnson & Johnson; Speaker Bureau/Expert testimony: Clovis Oncology Italy S.r.l.; Research grant/Funding (self): MSD Italia S.r.l. J. Maenpaa: Honoraria (self): AstraZeneca; Honoraria (self): Orion Pharma; Honoraria (self): Clovis; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Tesaro/GSK. L.J. Willmott: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Clovis; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: GSK; Honoraria (self), Speaker Bureau/Expert testimony: Merck. N. Colombo: Honoraria (self), Travel/Accommodation/Expenses: PharmaMar; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): GSK/Tesaro; Honoraria (self): Clovis; Honoraria (self): Immunogen; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Biocad; Research grant/Funding (institution): Roche. C. Aghajanian: Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Immunogen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Clovis; Honoraria (self), Advisory/Consultancy: Eisai/Merck; Honoraria (self), Advisory/Consultancy: Mersana Therapeutics; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): AstraZeneca. F. Wu: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. L. Molinero: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. V. Khor: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. Y.G. Lin: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. S. Pignata: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): GSK; Honoraria (self): Clovis; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): PharmaMar; Research grant/Funding (institution): Pfizer. All other authors have declared no conflicts of interest.