A Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-stage Small-cell Lung Cancer

Abstract Introduction/Background This study assessed the checkpoint kinase 1 inhibitor, prexasertib, in patients with extensive-stage small-cell lung cancer (ED-SCLC). Patients and Methods This was a parallel-cohort phase II study of 105 mg/m2 prexasertib once every 14 days for patients who progressed after ≤2 prior therapies and had platinum-sensitive (Cohort 1) or platinum-resistant/platinum-refractory (Cohort 2) disease. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Exploratory endpoints included biomarker identification and assessment of an alternate regimen (Cohort 3: 40 mg/m2 days 1-3,14-day cycle). Results In Cohort 1 (n=58), ORR was 5.2%, DCR 31%, median PFS 1.41 months (95% CI 1.31, 1.64), and median OS 5.42 months (95% CI 3.75, 8.51). In Cohort 2 (n=60), ORR was 0%, DCR 20%, median PFS 1.36 months (95% CI 1.25, 1.45), and median OS 3.15 months (95% CI 2.27, 5.52). The most frequent all grade, related, treatment-emergent adverse events were neutrophil count decreased (Cohort 1: 69.6%, Cohort 2: 73.3%), platelet count decreased (Cohort 1: 51.8%, Cohort 2: 50.0%), white blood cell count decreased (Cohort 1: 28.6%, Cohort 2: 40.0%), and anemia (Cohort 1: 39.3%, Cohort 2: 28.3%). Eleven (19.6%) patients in Cohort 1 and 1 patient (1.7%) in Cohort 2 experienced grade ≥3 febrile neutropenia. Prexasertib pharmacokinetics were consistent with prior studies. Cohort 3 outcomes were similar to Cohorts 1 and 2. No actionable biomarkers were identified. Conclusion Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC.