BXQ-350 may alleviate symptoms of chemotherapy- induced peripheral neuropathy via modulation of S1P
| العنوان: | BXQ-350 may alleviate symptoms of chemotherapy- induced peripheral neuropathy via modulation of S1P |
|---|---|
| المؤلفون: | Robert Wesolowski, Anne M. Noonan, Richard Charles Curry, John Charles Morris, Carolyn Muller, Vinay K. Puduvalli, Olivier Rixe, John L. Villano, Trisha Michel Wise-Draper, Emrullah Yilmaz, Gilles Tapolsky, Ray Takigiku |
| المصدر: | Journal of Clinical Oncology. 41:93-93 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cancer Research, Oncology |
| الوصف: | 93 Background: Chemotherapy Induced Peripheral Neuropathy (CIPN) is a debilitating side effect associated with many chemotherapeutic agents. It significantly impacts quality of life during treatment, causes lasting neuropathy, and may also shorten the treatment regimen, potentially impacting clinical benefit. The pathology of CIPN is still not completely understood, however, increasing evidence suggests sphingosine-1-phosphate (S1P) may be an important signaling molecule. Altered neuronal sphingolipid metabolism has been linked to neuropathic pain, evidenced by elevated plasma levels of S1P in patients receiving chemotherapy. Methods: BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that lowers systemic S1P. BXQ-350 was investigated in an adult Phase 1 dose-escalation safety study in heavily pretreated all-comer cancer patients with advanced solid malignancies ( NCT02859857 ). The primary objective was to determine the safety profile and potential clinical activity of BXQ-350 as monotherapy. Samples were collected to explore potential biomarkers. Results: BXQ-350 was safe and well tolerated. Clinical signs of activity were observed in 13 patients (~17.8% of evaluable patients) experiencing a clinical benefit (PR, SD) up to cycle 6 and beyond including: 4 CRC, 1 pancreatic, and 1 GIST patient. Two patients are still on study six years after enrollment, including 1 CRC. Interestingly, a pancreatic cancer patient with chronic CIPN at time of enrollment spontaneously reported a significant improvement of her neuropathic symptoms shortly after receiving BXQ-350. Investigation of potential improvements in patients with chronic CIPN at time of enrollment revealed that 4 out of 10 patients experienced an improvement of their symptoms that seemed to be associated with a decrease in S1P systemic levels following BXQ-350 administration. BXQ-350 was subsequently investigated in a murine oxaliplatin-CIPN preclinical model with results showing a dose-dependent prevention/resolution of CIPN correlating with decreasing systemic S1P levels. Conclusions: Results of this Phase 1 study in heavily pretreated patients shows that BXQ-350 was well tolerated and seems to generate a clinical benefit via modulation of S1P. There were preliminary signs that BXQ-350 may alleviate symptoms of CIPN in relation to decreasing S1P concentration. Additional studies are underway to better understand this novel mechanism of action. Clinical trial information: 02859857 . |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::b600926c79eca1d6fda41b258b751e73Test https://doi.org/10.1200/jco.2023.41.4_suppl.93Test |
| رقم الانضمام: | edsair.doi...........b600926c79eca1d6fda41b258b751e73 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
|---|