Nuvalent, Inc. announced an upcoming preclinical data poster presentation supporting the ongoing clinical development of its ALK-selective inhibitor, NVL-655. The data, resulting from a collaboration with the Yonsei University College of Medicine, will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19 in Orlando, Florida. The poster describes the preclinical intracranial antitumor activity of NVL-655 in a brain-implanted xenograft model derived from a patient with lung cancer harboring the alectinib-resistant EML4-ALK v3 G1202R mutation.

The poster additionally expands the characterization of NVL-655 alongside other ALK inhibitors. NVL-655 has previously demonstrated intracranial efficacy in a cell line-derived xenograft model as well as broad preclinical activity across diverse ALK resistance mutations and tumor types while maintaining high selectivity for ALK over TRKB. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

Details for the poster presentation are as follows: Title: Preclinical intracranial activity of NVL-655 in an alectinib-resistant patient-derived model harboring EML4-ALK fusion with G1202R mutation; Authors: Jii Bum Lee, Mi Ra Yu, Mi Ran Yun, You Won Lee, Seung Yeon Oh, Eun Ji Lee, Anupong Tangpeerachaikul, Henry E. Pelish, Byoung Chul Cho; Presenter: Anupong Tangpeerachaikul, Ph.D.; Permanent Abstract: 4022; Session Category: Experimental and Molecular Therapeutics; Session Title: Tyrosine Kinase and Phosphatase Inhibitors 1; Session Date and Time: April 18, 2023 from 9:00 a.m. – 12:30 p.m. ET; Location: Orange County Convention Center, Poster Section 20. NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R /L1196M ("GRLM"), G1202R /G1269A ("GRGA"), or G1202R /L1198F ("GRLF").

NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.