Yuping Sun, Jia Zhong, Huiwen Sun, Graeme Parr, Edit Lukacs, Daniel Slade, Yizhao Zhou, Xiaoyu Ren, David Kirk, Aleksandra Kmieciak, Tingting Yao, Jie Wang
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引用次数: 0
Abstract
Introduction: This phase I, multicenter, nonrandomized open-label study is the first study to investigate the safety, pharmacokinetics, and antitumor activity of ceralasertib, an oral ATR kinase inhibitor, in combination with durvalumab in Chinese patients with advanced solid tumors who are refractory or resistant to prior anti-PD-(L)1 immunotherapy or for whom no standard of care exists.
Methods: Patients were enrolled into one of two cohorts. Cohort 1 received ceralasertib 240 mg twice daily on days 1‒7 of cycle 0 then on days 22‒28 from cycle 1 onwards (28-day cycle). Cohort 2 received ceralasertib 160 mg twice daily on days 1‒14 of cycle 0 then on days 15‒28 from cycle 1 onwards (28-day cycle). All patients received durvalumab 1500 mg on day 1 (28-day cycle). Patients were treated until disease progression, discontinuation due to adverse events, or patient or investigator's decision to withdraw. The primary endpoint was safety and tolerability of ceralasertib combined with durvalumab. Secondary endpoints included ceralasertib pharmacokinetics and antitumor activity.
Results: Overall, 14 patients were enrolled (cohort 1, n = 8; cohort 2, n = 6). All patients were Chinese and the majority (85.7%) had received > 4 prior lines of therapy. Most patients (13/14; 92.9%) had an adverse event, which were grade ≥ 3 in 7 (50.0%) patients. No dose-limiting toxicities occurred (12 evaluable patients; six in each cohort). Pharmacokinetics for ceralasertib were comparable to that reported in other studies for monotherapy or in combination with durvalumab. Among 13 response-evaluable patients, 3/13 had a confirmed partial response (one with lung adenocarcinoma, one with squamous cell carcinoma of the cervix uteri, and one with lung squamous cell carcinoma); the objective response rate was 23.1% [80% CI 8.8‒44.4%]).
Conclusions: Ceralasertib plus durvalumab had antitumor activity in Chinese patients with advanced solid tumors; safety and pharmacokinetics were consistent with studies in Western patient populations.
期刊介绍：
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Aims and Scope
Oncology and Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Oncology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
Rapid Publication
The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of clinical therapies.
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The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts.
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Oncology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’.
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Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria.
At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision.
Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case by case basis and should be sent to the journal editor.
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Oncology and Therapy''s content is published open access under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0
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Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of £3650/€4500/$5100. The journal will consider fee discounts for developing countries and this is decided on a case by case basis.
Open Access
All articles published by Oncology and Therapy are published open access
Contact
For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.
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