دورية أكاديمية
Phase 1 study of the pan-RAF inhibitor tovorafenib in patients with advanced solid tumors followed by dose expansion in patients with metastatic melanoma
| العنوان: | Phase 1 study of the pan-RAF inhibitor tovorafenib in patients with advanced solid tumors followed by dose expansion in patients with metastatic melanoma |
|---|---|
| المؤلفون: | Rasco, Drew W., Medina, Theresa, Corrie, Pippa, Pavlick, Anna C., Middleton, Mark R., Lorigan, Paul, Hebert, Chris, Plummer, Ruth, Larkin, James, Agarwala, Sanjiv S., Daud, Adil I., Qiu, Jiaheng, Bozon, Viviana, Kneissl, Michelle, Barry, Elly, Olszanski, Anthony J. |
| بيانات النشر: | Springer Berlin Heidelberg Cancer Chemotherapy and Pharmacology |
| سنة النشر: | 2023 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Phase 1, Pan-RAF inhibitor, Melanoma, BRAF, Tovorafenib |
| الوصف: | Acknowledgements: Medical writing support was provided by Sandya Govinda Raju of Day One Biopharmaceuticals and Jim Heighway of Cancer Communications and Consultancy Ltd (Plumley, UK), with funding from Day One. ; Funder: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited ; Purpose: Genomic alterations of BRAF and NRAS are oncogenic drivers in malignant melanoma and other solid tumors. Tovorafenib is an investigational, oral, selective, CNS-penetrant, small molecule, type II pan‑RAF inhibitor. This first-in-human phase 1 study explored the safety and antitumor activity of tovorafenib. Methods: This two-part study in adult patients with relapsed or refractory advanced solid tumors included a dose escalation phase and a dose expansion phase including molecularly defined cohorts of patients with melanoma. Primary objectives were to evaluate the safety of tovorafenib administered once every other day (Q2D) or once weekly (QW), and to determine the maximum-tolerated and recommended phase 2 dose (RP2D) on these schedules. Secondary objectives included evaluation of antitumor activity and tovorafenib pharmacokinetics. Results: Tovorafenib was administered to 149 patients (Q2D n = 110, QW n = 39). The RP2D of tovorafenib was defined as 200 mg Q2D or 600 mg QW. In the dose expansion phase, 58 (73%) of 80 patients in Q2D cohorts and 9 (47%) of 19 in the QW cohort had grade ≥ 3 adverse events. The most common of these overall were anemia (14 patients, 14%) and maculo-papular rash (8 patients, 8%). Responses were seen in 10 (15%) of 68 evaluable patients in the Q2D expansion phase, including in 8 of 16 (50%) patients with BRAF mutation-positive melanoma naïve to RAF and MEK inhibitors. In the QW dose expansion phase, there were no responses in 17 evaluable patients with NRAS mutation-positive melanoma naïve to RAF and MEK inhibitors; 9 patients (53%) had a best response of stable disease. QW dose administration was associated with minimal accumulation of tovorafenib in ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; application/zip; text/xml |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/361733Test |
| الإتاحة: | https://www.repository.cam.ac.uk/handle/1810/361733Test |
| رقم الانضمام: | edsbas.5BAE3F50 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |