Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma

Publication Date:
2018-07-17
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
http://www.aacr.org/
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autor Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
beschreibung 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/m 2 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 + partial response + 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) = 15%], and three patients with SCCHN had partial response (ORR = 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/m 2 was confirmed as the recommended phase II dose. Clin Cancer Res; 24(14); 3263–72. ©2018 AACR .
citation_standardnr 6304540
datenlieferant ipn_articles
feed_id 9363
feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-07-17
journaleissn 1557-3265
journalissn 1078-0432
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Clinical Cancer Research
relation http://clincancerres.aacrjournals.org/cgi/content/short/24/14/3263?rss=1
search_space articles
shingle_author_1 Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
shingle_author_2 Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
shingle_author_3 Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
shingle_author_4 Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
shingle_catch_all_1 Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
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/m 2 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 + partial response + 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) = 15%], and three patients with SCCHN had partial response (ORR = 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/m 2 was confirmed as the recommended phase II dose. Clin Cancer Res; 24(14); 3263–72. ©2018 AACR .
Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
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/m 2 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 + partial response + 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) = 15%], and three patients with SCCHN had partial response (ORR = 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/m 2 was confirmed as the recommended phase II dose. Clin Cancer Res; 24(14); 3263–72. ©2018 AACR .
Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
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/m 2 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 + partial response + 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) = 15%], and three patients with SCCHN had partial response (ORR = 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/m 2 was confirmed as the recommended phase II dose. Clin Cancer Res; 24(14); 3263–72. ©2018 AACR .
Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
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/m 2 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 + partial response + 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) = 15%], and three patients with SCCHN had partial response (ORR = 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/m 2 was confirmed as the recommended phase II dose. Clin Cancer Res; 24(14); 3263–72. ©2018 AACR .
Hong, D. S., Moore, K., Patel, M., Grant, S. C., Burris, H. A., William, W. N., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., Zhang, W., Martinez, R., Wijayawardana, S., Beckmann, R., Lin, A. B., Eng, C., Bendell, J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
shingle_title_2 Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
shingle_title_3 Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
shingle_title_4 Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
timestamp 2025-06-30T23:36:07.002Z
titel Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
titel_suche Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma
topic WW-YZ
uid ipn_articles_6304540