Phase II study to evaluate safety and efficacy of MEDI4736 (durvalumab) + radiotherapy in patients with newly diagnosed unmethylated MGMT glioblastoma (new unmeth GBM)

• Published in: Journal of clinical oncology Vol. 37; no. 15_suppl; p. 2032
• Main Authors: Reardon, David A., Kaley, Thomas Joseph, Dietrich, Jorg, Clarke, Jennifer Leigh, Dunn, Gavin, Lim, Michael, Cloughesy, Timothy Francis, Gan, Hui Kong, Park, Andrew J., Schwarzenberger, Paul, Ricciardi, Toni, Macri, Mary J., Ryan, Aileen, Venhaus, Ralph Rudolph
• Format: Journal Article
• Language: English
• Published: 20.05.2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.15_suppl.2032

Abstract only 2032 Background: Durvalumab (durva), a human IgG1 monoclonal Ab against PD-L1, is FDA-approved for selected patients with bladder and non-small cell lung cancers. PD-L1 is expressed by some GBM tumors, while GBM infiltrating T lymphocytes often express PD-1. Radiation induced cell death releases tumor antigens and could potentiate anti-PD-(L)1 therapy. Methods: This ongoing Phase 2 open-label study (NCT02336165) evaluates the safety and efficacy of durva (10 mg/kg every 2 weeks) in 5 GBM cohorts. Results are presented for Cohort A, which evaluates durva + standard radiotherapy (RT, 60 Gy over 30 fractions) followed by durva monotherapy in patients with new unmeth GBM after maximum safe resection. The primary efficacy endpoint for Cohort A is overall survival at 12 months (OS12); secondary endpoints include safety/tolerability, tumor response rate, and progression-free survival (PFS). Historical benchmarks of median OS and OS12 for patients with new unmeth GBM following standard therapy are 12.7 months and 50%, respectively (EORTC 26981-22981/NCIC CE.3). Results: Median follow-up of 40 enrolled patients is 24.5 months (data cutoff = 05 Nov 2018). Baseline characteristics: male, 70%; median age, 57.0 [22 to 77] years; ECOG PS0, 60.0%; ECOG PS1, 40.0%; measurable disease, 80.0%; and dexamethasone use, 32.5%. Treatment-related adverse events with maximum CTCAE grade ≥ 3 occurred in 14 (35.0%) patients; the most common were asymptomatic increased lipase (n = 6) and increased amylase (n = 2). Twenty-four of 40 patients were alive at 12 months (Kaplan-Meier for OS12, 60.0% [90% CI: 46.1, 71.4]). Median OS was 15.1 (95% CI: 12.0, 18.4) months. As of 05 Nov 2018, 8 (20%) patients remain alive, with ongoing survival ranging from 15.7 to 34.9 months. Tumor immunocorrelative and systemic studies are pending. Conclusions: This is the first study report of anti-PD-L1 for new GBM. Durva was well tolerated when combined with RT and seemed to have efficacy among patients with new unmeth GBM. Further studies may be warranted. Clinical trial information: NCT02336165.