TY - JOUR
T1 - Evaluation of prexasertib, a checkpoint kinase 1 inhibitor, in a phase ib study of patients with squamous cell carcinoma
AU - Hong, David S.
AU - Moore, Kathleen
AU - Patel, Manish
AU - Grant, Stefan C.
AU - Burris, Howard A.
AU - William Jr, William Nassib
AU - Jones, Suzanne
AU - Meric-Bernstam, Funda
AU - Infante, Jeffrey
AU - Golden, Lisa
AU - Zhang, Wei
AU - Martinez, Ricardo
AU - Wijayawardana, Sameera
AU - Beckmann, Richard
AU - Lin, Aimee Bence
AU - Eng, Cathy
AU - Bendell, Johanna
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/7/15
Y1 - 2018/7/15
N2 - Purpose: Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. Patients and Methods: Patients were given prexasertib 105 mg/m2 as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed. Results: Prexasertib was given to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and neck (SCCHN), and 16 with squamous cell non–small cell lung cancer (sqNSCLC). Patients were heavily pretreated (49% 3 prior regimens). The most common treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients had febrile neutropenia. Median progression-free survival was 2.8 months [90% confidence interval (CI), 1.9–4.2] for SCC of the anus, 1.6 months (90% CI, 1.4–2.8) for SCCHN, and 3.0 months (90% CI, 1.4–3.9) for sqNSCLC. The clinical benefit rate at 3 months (complete response þ partial response þ stable disease) across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four patients with SCC of the anus had partial or complete response [overall response rate (ORR) ¼ 15%], and three patients with SCCHN had partial response (ORR ¼ 5%). Biomarker analyses focused on genes that altered DNA damage response or increased replication stress. Conclusions: Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m2 was confirmed as the recommended phase II dose.
AB - Purpose: Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. Patients and Methods: Patients were given prexasertib 105 mg/m2 as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed. Results: Prexasertib was given to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and neck (SCCHN), and 16 with squamous cell non–small cell lung cancer (sqNSCLC). Patients were heavily pretreated (49% 3 prior regimens). The most common treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients had febrile neutropenia. Median progression-free survival was 2.8 months [90% confidence interval (CI), 1.9–4.2] for SCC of the anus, 1.6 months (90% CI, 1.4–2.8) for SCCHN, and 3.0 months (90% CI, 1.4–3.9) for sqNSCLC. The clinical benefit rate at 3 months (complete response þ partial response þ stable disease) across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four patients with SCC of the anus had partial or complete response [overall response rate (ORR) ¼ 15%], and three patients with SCCHN had partial response (ORR ¼ 5%). Biomarker analyses focused on genes that altered DNA damage response or increased replication stress. Conclusions: Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m2 was confirmed as the recommended phase II dose.
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U2 - 10.1158/1078-0432.CCR-17-3347
DO - 10.1158/1078-0432.CCR-17-3347
M3 - Article
C2 - 29643063
AN - SCOPUS:85050080469
SN - 1078-0432
VL - 24
SP - 3263
EP - 3272
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -