Nuvalent Announces Positive Topline Pivotal Data from ALKOVE-1 Clinical Trial of Neladalkib for TKI Pre-treated Patients with Advanced ALK-positive NSCLC

Core Insights - Nuvalent, Inc. announced positive topline pivotal data for neladalkib, an investigational ALK-selective inhibitor, in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who have been pre-treated with tyrosine kinase inhibitors (TKIs) [1][2][3] Group 1: Clinical Trial Data - The ALKOVE-1 Phase 1/2 clinical trial is evaluating neladalkib in patients with advanced ALK-positive NSCLC, with a recommended Phase 2 dose (RP2D) of 150 mg once daily established during the Phase 1 dose-escalation [3][27] - In the pivotal analysis of 253 TKI pre-treated patients, the objective response rate (ORR) was 31% with a 95% confidence interval (CI) of 26% to 37% [5][7] - Among 63 lorlatinib-naïve patients, the ORR was 46% with a 95% CI of 33% to 59% [5][9] - The durability of response (DOR) at 12 months was 64% for the overall population and 80% for the lorlatinib-naïve subset [5][9] Group 2: Safety Profile - Neladalkib demonstrated a well-tolerated safety profile, with treatment-emergent adverse events (TEAEs) leading to dose reductions in 17% of patients and discontinuation in 5% [21][23] - The most common TEAEs included increased alanine aminotransferase (47%) and aspartate aminotransferase (44%) [21][22] Group 3: Future Plans - The company plans to discuss the pivotal data with the FDA at a pre-New Drug Application (NDA) meeting and will present detailed study results at a future medical meeting [23][24] - Global enrollment for TKI-naïve patients is ongoing in the ALKAZAR Phase 3 trial, which compares neladalkib to alectinib [19][28] Group 4: Background on Neladalkib - Neladalkib is designed to penetrate the brain and selectively inhibit ALK, aiming to overcome resistance seen with existing ALK inhibitors and to minimize adverse events associated with dual TRK/ALK inhibitors [26][29]