Nuvalent Initiates the Phase 2 Portion of ARROS-1 Clinical Trial for Patients with ROS1-Positive NSCLC and other Solid Tumors
Wednesday, September 06, 2023
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 initiation of the Phase 2 portion of ARROS-1, its Phase 1/2 clinical trial of NVL-520 for patients with ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumors, following alignment with the US Food and Drug Administration (FDA) on a recommended Phase 2 dose (RP2D) of 100 mg daily.
NVL-520 is a novel brain-penetrant ROS1-selective tyrosine kinase inhibitor (TKI) created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, off-target central nervous system (CNS) adverse events associated with TRK inhibition, and brain metastases that may limit the use of currently available ROS1 TKIs.
"The ARROS-1 trial was designed to support a seamless transition from first-in-human dose-exploration in a heavily pre-treated population to a Phase 2 portion designed with the potential to support registration. We are thrilled to achieve this milestone towards our goal of bringing a potential best-in-class therapy to patients with ROS1-positive NSCLC as efficiently as possible," said Darlene Noci, A.L.M., Chief Development Officer at Nuvalent.
"The Phase 2 portion of the ARROS-1 trial includes multiple cohorts which enable the parallel investigation of NVL-520 for patients with ROS1-positive NSCLC who are either TKI naïve or pre-treated with a ROS1 TKI," Ms. Noci continued. "Support for the Phase 2 cohort design includes the demonstrated nonclinical activity of NVL-520 in the periphery and in the CNS, and its selective inhibition of ROS1 and ROS1 drug-resistance mutant G2032R over the structurally-related TRK kinases. Combined with the broad clinical activity and favorable tolerability observed to date in heavily pre-treated patients in the Phase 1 portion of ARROS-1, we believe there is the potential for NVL-520 to provide durable responses while minimizing adverse events and dose limiting toxicities for patients with ROS1-positive cancers throughout the treatment paradigm."
In the Phase 1 portion of ARROS-1, six dose levels (25 mg to 150 mg daily) of NVL-520 were evaluated in heavily pre-treated patients with ROS1-positive solid tumors. A maximum tolerated dose (MTD) was not reached, and no clinically significant exposure-response relationships for safety and efficacy were observed across the dose levels evaluated. The RP2D of 100 mg daily maintained steady state plasma levels above all target efficacy thresholds (ROS1 wild type and ROS1 G2032R in both the periphery and in the CNS).
"With the advancement of the first of our parallel lead programs into a Phase 2 trial with registrational intent, the Nuvalent team demonstrates its continued ability to scale while maintaining ambitious timelines towards our goal of delivering precisely targeted therapies to patients with cancer," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "We look forward to providing an update from the ARROS-1 trial at a medical meeting in 2024."
About Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent is advancing a robust pipeline with parallel lead programs in ROS1-positive and ALK-positive non-small cell lung cancer (NSCLC), a program in HER2 Exon 20 insertion-positive cancers, and multiple discovery-stage research programs. We routinely post information that may be important to investors on our website at www.nuvalent.com. Follow us on Twitter (@nuvalent) and LinkedIn.
