Phase I/Ib Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma
| العنوان: | Phase I/Ib Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma |
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| المؤلفون: | Srikant Viswanadha, Sumana Devata, Ramchandren Radhakrishnan, Swaminathan P. Iyer, Lauren C. Pinter-Brown, Swaroop Vakkalanka, Ajit Nair, Neil J. Korman, Mary Jo Lechowicz, Yasuhiro Oki, Auris Huen, Prajak J Barde, Jasmine Zain, Bradley M. Haverkos, Kasi V. Routhu |
| المصدر: | Cancers, Vol 12, Iss 2293, p 2293 (2020) Cancers Volume 12 Issue 8 |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, medicine.medical_specialty, PTCL, CD30, Gastroenterology, lcsh:RC254-282, Article, Transaminase, Romidepsin, 03 medical and health sciences, 0302 clinical medicine, CTCL, Pharmacokinetics, Refractory, Internal medicine, medicine, T-cell lymphoma, Adverse effect, maximum tolerated dose, business.industry, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Lymphoma, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, dose limiting toxicity, business, medicine.drug |
| الوصف: | Tenalisib (RP6530), a dual phosphoinositide 3-kinase &delta /&gamma inhibitor was evaluated in a phase I/Ib study for maximum tolerated dose (MTD), pharmacokinetics, and efficacy in patients with relapsed/refractory peripheral and cutaneous T-Cell Lymphoma (TCL). Histologically confirmed (TCL) patients, with &ge 1 prior therapy received Tenalisib orally in a 28-day cycle in doses of 200 to 800 mg twice daily (800 mg in fasting and fed state) in escalation phase (n = 19) and 800 mg twice daily (fasting) in expansion phase (n = 39). The most frequently reported treatment emergent adverse events (TEAE) and related TEAE were fatigue (45%) and transaminase elevations (33%), respectively. Most frequently reported related Grade &ge 3 TEAE was transaminase elevation (21%). Two dose-limiting toxicities occurred in the 800 mg fed cohort hence, 800 mg fasting dose was deemed MTD. Tenalisib was absorbed rapidly with a median half-life of 2.28 h. Overall response rate in 35 evaluable patients was 45.7% (3 complete response (CR) 13 partial response (PR)) and median duration of response was 4.9 months. Responding tumors showed a marked downregulation of CD30, IL-31 and IL-32&alpha With an acceptable safety and promising clinical activity, Tenalisib can be a potential therapeutic option for relapsed/refractory TCL. Currently, a phase I/II combination study with romidepsin is ongoing. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae583485aa89d38a820914ebe5f02060 https://www.mdpi.com/2072-6694/12/8/2293 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ae583485aa89d38a820914ebe5f02060 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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