81TiP NVL-655, a selective anaplastic lymphoma kinase (ALK) inhibitor, in patients with advanced ALK-positive solid tumors: The phase I/II ALKOVE-1 study
Recommended Citation
Johnson ML, Ou SHI, Felip E, Baik C, Besse B, Mazieres J, Camidge DR, Gadgeel S, Drilon A, Elamin YY, Liu G, Reuss JE, Kehrig T, Pelish HE, Zhu V, and Lin JJ. 81TiP NVL-655, a selective anaplastic lymphoma kinase (ALK) inhibitor, in patients with advanced ALK-positive solid tumors: The phase I/II ALKOVE-1 study. J Thorac Oncol 2023; 18(4):S86-S87.
Document Type
Conference Proceeding
Publication Date
4-1-2023
Publication Title
J Thorac Oncol
Abstract
Background: Aberrations of the ALK oncogene drive tumor cell proliferation, survival, and metastasis in multiple adult and pediatric cancers. ALK gene fusions are detected in ~5% of advanced non-small cell lung cancers (NSCLC); among these patients, the incidence of central nervous system (CNS) metastases at diagnosis is ~40%. Although 5 tyrosine kinase inhibitors (TKIs) are approved by the FDA and EMA for ALK-positive NSCLC, therapeutic limitations remain, such as acquired resistance due to secondary and compound ALK mutations and/or neurologic adverse events attributed to off-target inhibition of TRK. NVL-655 is a novel, brain-penetrant ALK-selective TKI that exhibits preclinical activity against diverse ALK fusions and mutations, including G1202R and G1202R compound mutations, while sparing inhibition of TRK. The ALKOVE-1 study is evaluating the safety and preliminary activity of NVL-655 in patients with solid tumors harboring oncogenic ALK alterations, including those with acquired ALK resistance mutations and CNS metastases. Trial design ALKOVE-1 consists of a phase I dose escalation followed by a phase II expansion in cohorts defined by tumor type and prior therapies. Phase I includes adult patients with any solid tumor type harboring an oncogenic ALK gene fusion or activating mutation (by local testing), including ALK fusion-positive NSCLC after ≥ 1 prior 2nd or 3rd generation ALK TKI. Prior platinum-based chemotherapy and/or immunotherapy, CNS disease without progressive neurological symptoms or increasing corticosteroid doses, and evaluable but non-measurable disease are allowed. Patients will receive NVL-655 by daily oral administration. Primary phase I objectives are to determine the NVL-655 recommended phase II dose and, if applicable, maximum tolerated dose. Additional objectives include evaluation of safety/ tolerability, preliminary activity, and characterization of the pharmacokinetic and pharmacodynamic profiles of NVL-655. Longitudinal analysis of circulating tumor DNA will be performed, including ALK mutation profiling and other relevant biomarkers. The phase I portion of the study is ongoing. Clinical trial identification NCT05384626 (May 20, 2022).
Volume
18
Issue
4
First Page
S86
Last Page
S87