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

Byers, Lauren Averett and Navarro, Alejandro and Schaefer, Eric and Johnson, Melissa and Özgüroglu, Mustafa and Han, Ji-Youn and Bondarenko, Igor and Cicin, Irfan and Dragnev, Konstantin H. and Abel, Adam and Wang, Xuejing and McNeely, Samuel and Hynes, Scott and Lin, Aimee Bence and Forster, Martin (2021) A Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-Stage Small-Cell Lung Cancer. Clinical Lung Cancer, 000 (000). pp. 1-10. ISSN 1525-7304 (print), 1938-0690 (online)

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Abstract

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. Background: This study assessed the checkpoint kinase 1 inhibitor prexasertib in patients with extensive-stage smallcell 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 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). Results: 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. Conclusion: Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC.

Item Type:	Article
Additional Information:	https://doi.org/10.1016/j.cllc.2021.04.005 Available online 24 April 2021 In Press, Corrected Proof https://www.scopus.com/inward/record.uri?eid=2-s2.0-85106618250&doi=10.1016%2fj.cllc.2021.04.005&partnerID=40&md5=3a9a54e38fbecfbba8bf08638c5d86be open access
Uncontrolled Keywords:	Biomarker; Checkpoint kinase 1 inhibitor; Pharmacokinetics; Refractory; Relapsed; Small cell lung cancer
Subjects:	Oncology
Divisions:	Departments > Department of Oncology and Medical Radiology
Depositing User:	Елена Шрамко
Date Deposited:	08 Jun 2021 10:11
Last Modified:	08 Jun 2021 10:20
URI:	http://repo.dma.dp.ua/id/eprint/6630

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