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

• Published in: Clinical lung cancer Vol. 22; no. 6; pp. 531 - 540
• Main Authors: Byers, Lauren Averett, Navarro, Alejandro, Schaefer, Eric, Johnson, Melissa, Özgüroğlu, Mustafa, Han, Ji-Youn, Bondarenko, Igor, Cicin, Irfan, Dragnev, Konstantin H., Abel, Adam, Wang, Xuejing, McNeely, Samuel, Hynes, Scott, Lin, Aimee Bence, Forster, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2021
• Subjects: Aged; Aged, 80 and over; Biomarker; Checkpoint kinase 1 inhibitor; Female; Humans; Lung Neoplasms - pathology; Male; Middle Aged; Pharmacokinetics; Protein Kinase Inhibitors - therapeutic use; Pyrazines - therapeutic use; Pyrazoles - therapeutic use; Refractory; Relapsed; Small cell lung cancer; Small Cell Lung Carcinoma - drug therapy; Small Cell Lung Carcinoma - pathology; Treatment Outcome; Refractory; Checkpoint kinase 1 inhibitor; Small cell lung cancer; Biomarker; Pharmacokinetics; Relapsed
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2021.04.005

This study assessed the checkpoint kinase 1 inhibitor prexasertib in patients with extensive-stage small-cell lung cancer (ED-SCLC). This was a parallel-cohort phase II study of 105 mg/m2 prexasertib once every 14 days for patients who progressed after no more than two 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 alternative regimen (Cohort 3: 40 mg/m2 days 1-3, 14-day cycle). In Cohort 1 (n = 58), ORR was 5.2%; DCR, 31%; median PFS, 1.41 months (95% confidence interval [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 decreased neutrophil count (Cohort 1, 69.6%; Cohort 2, 73.3%), decreased platelet count (Cohort 1, 51.8%; Cohort 2, 50.0%), decreased white blood cell count (Cohort 1, 28.6%; Cohort 2, 40.0%), and anemia (Cohort 1, 39.3%; Cohort 2, 28.3%). Eleven patients (19.6%) in Cohort 1 and one patient (1.7%) in Cohort 2 experienced grade ≥3 febrile neutropenia. Prexasertib pharmacokinetics were consistent with prior studies. Cohort 3 outcomes were similar to those of Cohorts 1 and 2. No actionable biomarkers were identified. Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC. Patients with extensive-stage small-cell lung cancer (ED-SCLC) need improved outcomes in the relapsed/refractory setting. This phase II study evaluated the safety and efficacy of prexasertib, a checkpoint kinase 1 inhibitor, in platinum-sensitive and platinum-refractory ED-SCLC. Prexasertib demonstrated response rates of 5.2% in platinum-sensitive and 0% in platinum-refractory ED-SCLC. Prexasertib did not show prespecified efficacy as monotherapy in ED-SCLC.