2022 World Conference on Lung Cancer (ePosters)-EP08.02-041. NVL-520, a Highly Selective ROS1 Inhibitor, in Patients with Advanced ROS1-Positive Solid Tumors: The Phase 1/2 ARROS-1 Study

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The Phase 1/2 ARROS-1 study is evaluating the safety and effectiveness of NVL-520, a selective inhibitor of the ROS1 gene, in patients with advanced ROS1-positive solid tumors. The study aims to determine the recommended dose and maximum tolerated dose of NVL-520, as well as evaluate its safety, pharmacokinetics, and preliminary effectiveness.<br /><br />The study is for adults with solid tumors that have a ROS1 gene fusion and have previously received either a ROS1 TKI for NSCLC or systemic anticancer therapy for other solid tumors. Patients with stable central nervous system disease are eligible to participate. Tumors with other oncogenic driver alterations are not allowed.<br /><br />Up to 54 patients will be enrolled in the study, with additional patients allowed at previously-evaluated doses for dose optimization. The main goals of the study are to determine the recommended dose and identify the maximum tolerated dose based on dose-limiting toxicity. Secondary objectives include evaluating safety, pharmacokinetics, preliminary effectiveness, and intracranial activity.<br /><br />The treatment involves taking NVL-520 orally once a day until intolerance or disease progression. Safety will be assessed through various tests and examinations, and tumors will be evaluated using standard criteria, including brain imaging for all patients at the start of the study.<br /><br />NVL-520 has shown activity in inhibiting ROS1 and ROS1 G2032R in preclinical models. The study aims to demonstrate its potential in minimizing adverse events and producing lasting responses in patients with ROS1 tumors, including those with resistance mutations and brain metastases.<br /><br />Overall, the ARROS-1 study is examining the safety and effectiveness of NVL-520 in patients with ROS1-positive solid tumors, with a focus on determining the recommended dose, maximum tolerated dose, and overall antitumor activity.<br /><br />In preclinical studies, NVL-520 has shown potency in targeting ROS1 fusions and drug-resistant mutations, including the G2032R mutation. It has demonstrated activity against ROS1 tumors in cell and animal models, including CNS metastases. NVL-520 has higher selectivity for ROS1 over other kinases, reducing the risk of neurological adverse events compared to dual TRK/ROS1 inhibitors.<br /><br />These findings suggest that NVL-520 may be a promising treatment option for patients with ROS1-positive cancers, including those with acquired resistance mutations. Clinical trials are currently ongoing to investigate its potential.

Asset Subtitle

Alexander Drilon

Meta Tag

Speaker Alexander Drilon

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

ARROS-1 study

NVL-520

ROS1 gene

solid tumors

safety

effectiveness

recommended dose

maximum tolerated dose

pharmacokinetics

preliminary effectiveness