[ad_1]
Favorable preliminary safety profile of NVL-520 suggests potential for a highly ROS1-selective, TRK
sparing design, with no dose-limiting toxicities, treatment-related serious adverse events, treatment-
related dizziness, or adverse events leading to treatment reductions or discontinuations as of the
data cut-off date
Encouring preliminary signs of activity observed across all dose levels in heavily pre-treated
patients with ROS1-positive NSCLC, including in subgroups of patients with G2032R resistance
mutation or with brain metastases
Company to host conference call today at 8:30 am EDT
CAMBRIDGE, Mass., Oct. 28, 2022 /PRNewswire/ — Nuvalent, Inc. (NASDAQ:NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced the initial data from the Phase 1 dose-escalation portion of its ongoing ARROS-1 Phase 1/2 clinical trial of NVL-520 for patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumors. These data will be presented today in the “New Drugs on the Horizon” oral plenary session at the 34th EORTC-NCI-AACR (ENA) Symposium in Barcelona, Spain.
NVL-520 is a novel brain-penetrant ROS1-selective inhibitor created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, off-target central nervous system (CNS) adverse events, and brain metastases that may limit the use of currently available ROS1 tyrosine kinase inhibitors (TKIs).
“Currently approved and investigational ROS1 TKIs are important treatment options for advanced ROS1 fusion-positive cancers. However, these drugs can have key limitations. These include the inability to treat on-target resistance and brain metastases effectively, and an association with neurologic adverse events ,” said Alexander DrilonMD, Chief, Early Drug Development Service, Memorial Sloan Kettering Cancer Center (MSK) and presenting investigator. “These preliminary data support NVL-520 as a potential best-in-class ROS1-selective inhibitor that may combine, for the first time , potent and selective targeting of diverse ROS1 fusions and secondary ROS1 resistance mutations including G2032R, brain penetrance, and the avoidance of TRK inhibition that can be dose limiting.”
As of September 1, 202235 subjects have been enrolled in the Phase 1 portion of the ARROS-1 trial. Treatment with NVL-520 across five evaluated dose levels ranging from 25 mg once daily (QD) to 125 mg QD resulted in exposures above all target efficacy thresholds. As of the preliminary data cut-off date of September 13, 2022no dose-limiting toxicities (DLTs), treatment-related serious adverse events (SAEs), treatment-emergent dizziness, or adverse events leading to treatment reductions or discontinuations were observed.
Preliminary activity data reported as of the data cut-off date were available from 21 heavily pre-treated response-evaluable NSCLC patients, of which partial responses were observed in 48% (10/21). To evaluate key target characteristics of NVL-520 , activity was examined in subgroups including:
- Patients with ROS1 G2032R mutations (Objective Response Rate (ORR) 78%, 7/9);
- Patients with a history of CNS metastases (ORR 73%, 8/11);
- The most heavily pre-treated of patients, receiving two or more prior ROS1 TKIs and one or more prior lines of chemotherapy (ORR 53%, 9/17); and
- Patients previously treated with lorlatinib or repotrectinib (ORR 50%, 9/18).
As of the preliminary data cut-off date, 76% (16/21) of response-evaluable patients continued on NVL-520 treatment. Enrollment in the Phase 1 portion of the trial is ongoing.
“We are excited to present the first look at the safety and clinical activity of NVL-520 from our ARROS-1 clinical trial, which we believe supports NVL-520 as a potential best-in-class ROS1-selective inhibitor that may be capable of overcoming the limitations of current approved and investigational ROS1 TKIs,” said Christopher TurnerMD, Chief Medical Officer of Nuvalent. “Across all evaluated dose levels, NVL-520 exhibited activity in a heavily pre-treated patient population, many of whom have exhausted all available treatment options and would have been excluded from other investigational ROS1 TKI studies . Importantly, the favorable safety profile and lack of dose reductions or discontinuations due …
Full story available on Benzinga.com
[ad_2]
Source link
