Results from a phase 1/2 trial led by researchers at The University of Texas MD Anderson Cancer Center demonstrated that the targeted RAS inhibitor therapy daraxonelasib may improve patient outcomes over the current standard of care for patients with RAS-mutated pancreatic cancer.
This research today New England Medical Journalled by David Hong, MD, vice chair of Investigational Cancer Therapies. 38 patients received 300 mg. Daraxone lasib dosage. The response rate was 29% and median overall survival was 15.6 months, a significant improvement over previous response rates to second-line chemotherapy.
“This trial provides a very strong signal that this targeted therapy has the potential to extend overall survival in these patients,” Hong said. “The rapid and sustained response and manageable overall safety profile support continued evaluation of daraxone lasib.”
What is the significance of this study of dalaxone lasib for pancreatic cancer?
This study investigated daraxone lasib in pancreatic adenocarcinoma, which accounts for more than 90% of all pancreatic cancers. These are among the deadliest cancers because they are not diagnosed until the advanced stages, when available treatments are generally ineffective. Only about one-third of patients respond to first-line chemotherapy and less than 10% respond to chemotherapy as second-line treatment. Overall survival for these patients is only 5 to 7 months.
However, more than 90% of these cancers are caused by RAS mutations and may be treated with RAS-targeted therapies such as daraxone radib.
What other important data was obtained from this study?
The primary endpoint of this Phase 1/2 dose expansion and escalation study was safety. 96% of patients experienced side effects of any grade, but only 30% experienced grade 3 or higher side effects. The most common side effects were rash, diarrhea, mouth/throat inflammation (stomatitis, mucositis), and fatigue.
Half of the patients were treated with 300 mg. Levels had dose modifications, but no patients had to discontinue treatment due to side effects. It is noteworthy that current second-line chemotherapy also has significant negative effects on patients.
What makes Daraxone Radib different from other treatments that target RAS mutations?
Mutations in RAS proteins such as KRAS are known to cause several types of cancer, and multiple types of mutations exist. The most commonly targeted mutation is KRAS G12C, but while this particular mutation is relatively common in some types of cancer, it is relatively rare in pancreatic cancer. Additionally, most current RAS treatments target RAS mutations in the “off” state, whereas KRAS promotes pancreatic adenocarcinoma in the “on” state. Dalaxone lasib inhibits RAS in the “on” state and can target multiple RAS variants, suggesting that this type of therapy may be used more often in the treatment of pancreatic cancer.
Early data from this trial, presented at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, led the FDA to grant orphan drug status to daraxone lasib and the ongoing Phase 3 RASolute trial.
sauce:
University of Texas MD Anderson Cancer Center
Reference magazines:
DOI: 10.1056/NEJMoa2505783
