Atim-38. Phase 2 Study to Evaluate the Clinical Efficacy and Safety of Medi4736 (durvalumab, Durva) + Bevacizumab (bev) in Bev-naïve Patients With Recurrent Glioblastoma (gbm)
Year: 2018
Type: conference-abstract
Abstract: Durva is a human IgG1 mAb against PD-L1. Blockade of PD-1/PD-L1 has shown benefit among solid tumors; data implicate PD-1/PD-L1 signaling as a significant contributor to immunosuppression in GBM. BEV is an approved angiogenesis inhibitor for recurrent GBM; angiogenesis inhibition may promote antitumor benefit of immunotherapies. A review showed that lower dose BEV resulted in longer PFS/OS than the standard. Ongoing Phase 2 open-label study (NCT02336165) evaluates safety and efficacy of durva (10mg/kg Q2W) in 5 GBM cohorts. Results are presented for Cohorts B2 (durva + BEV 10mg/kg Q2W) and B3 (durva +BEV 3mg/kg Q2W) in BEV-naïve recurrent GBM. Primary efficacy endpoint for Cohorts B2/B3 is 6-month progression-free survival (PFS6), by modified RANO per investigator assessment; secondary endpoints include safety/tolerability. Comparative benchmark for BEV in recurrent GBM is PFS6 of 42%. The null hypothesis (PFS6 ≤42%) was tested in Intent-to-Treat (ITT) population against the alternative hypothesis (PFS6 ≥62%). ITT includes patients receiving any dose of durva and having at least baseline and 1 post-baseline tumor assessment. Durva alone in Cohort B of this study demonstrated PFS6 of 20% (90% CI: 9.7, 33.0). As of 02Apr2018, 33 patients were treated in each cohort (B2, male: 54.5%, median age: 57.0 [40–74] years; B3, male: 60.6%, median age: 54.0 [23–73] years). Most common treatment-related adverse events (TRAEs, in ≥4 [12.1%] patients in either cohort): fatigue, dysphonia, increased ALT, AST, amylase, or lipase, diarrhea, hypertension, arthralgia, headache, and proteinuria. Incidences of TRAEs by maximum CTCAE grade (Gr) ≥3 for Cohorts B2/B3 were Gr3: 24.2/6.1%; Gr4: 0/6.1%; and Gr5: 0/0%. Kaplan-Meier estimate for PFS6 (n=33 each): B2, 15.2% (80% CI: 8.2, 24.0); B3, 21.1% (80% CI: 12.4, 31.4); 3 patients in each cohort showed partial response. The addition of durva to BEV did not improve on the outcome of durva alone.
Source: Neuro-Oncology
Institutions: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Massachusetts General Hospital, University of California, San Francisco, Washington University in St. Louis, Johns Hopkins Hospital, University of California, Los Angeles, Austin Hospital, Ludwig Cancer Research
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2900425127