التفاصيل البيبلوغرافية
| العنوان: |
ATR inhibitor, camonsertib, dose optimization in patients with biomarker-selected advanced solid tumors (TRESR study) |
| المؤلفون: |
Fontana, Elisa, Rosen, Ezra, Lee, Elizabeth K, Højgaard, Martin, Mettu, Niharika B, Lheureux, Stephanie, Carneiro, Benedito A, Cote, Gregory M, Carter, Louise, Plummer, Ruth, Mahalingam, Devalingam, Fretland, Adrian J, Schonhoft, Joseph D, Silverman, Ian M, Wainszelbaum, Marisa, Xu, Yi, Ulanet, Danielle, Koehler, Maria, Yap, Timothy A |
| المصدر: |
JNCI: Journal of the National Cancer Institute ; ISSN 0027-8874 1460-2105 |
| بيانات النشر: |
Oxford University Press (OUP) |
| سنة النشر: |
2024 |
| الوصف: |
Background Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus dose/schedule optimization requires extended follow-up to assess prolonged treatment effects. Methods Long-term safety/tolerability and antitumor efficacy of three camonsertib monotherapy dose levels/schedules were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on/4 off (160 3/4; the preliminary recommended phase II dose [RP2D]) and two step-down groups of 120 mg QD 3/4 (120 3/4) and 160 mg QD 3/4, 2 weeks on/1 off (160 3/4, 2/1w). Safety endpoints included incidence of treatment-related adverse events (TRAEs), dose modifications, and transfusions. Efficacy endpoints included overall response rate, clinical benefit rate, progression-free survival, and circulating-tumor-DNA (ctDNA)-based molecular response rate. Results The analysis included 119 patients: 160 3/4 (n = 67), 120 3/4 (n = 25), and 160 3/4, 2/1w (n = 27) treated up to 117.1 weeks as of the data cutoff. The risk of developing grade 3 anemia was significantly lower in the 160 3/4, 2/1w group compared with the preliminary RP2D group (HR = 0.23, 2-sided P = .02), translating to reduced transfusion and dose reduction requirements. The intermittent weekly schedule did not compromise antitumor activity. Conclusion The 160 3/4, 2/1w dose was established as an optimized regimen for future camonsertib monotherapy studies offering significantly reduced anemia incidence without any compromise to efficacy. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1093/jnci/djae098 |
| DOI: |
10.1093/jnci/djae098/57421115/djae098.pdf |
| الإتاحة: |
https://doi.org/10.1093/jnci/djae098Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.60A7113B |
| قاعدة البيانات: |
BASE |
