## Neladalkib Shows Promise in Advanced ALK-Positive NSCLC
Topline data from the ALKOVE-1 phase 1/2 clinical trial (NCT05384626) demonstrate neladalkib’s (NVL-655; Nuvalent) promise for treatment of patients with advanced ALK-positive non-small cell lung cancer (NSCLC) previously treated with tyrosine kinase inhibitors (TKI). The data showed an objective response rate (ORR) of 31% (95% CI: 26, 37), with an estimated durability of response of 64% and 53% at 12 and 18-months, respectively.1,2
ALK fusions are detected in approximately 1% to 4% of lung cancers, most often in adenocarcinomas. Although less common than other genetic alterations, they present a significant treatment challenge for affected patients.3
Neladalkib is a next-generation,brain-penetrant ALK inhibitor developed to address key shortcomings of the current ALK-targeted therapies. Its design allows it to stay effective even when tumors acquire resistance to earlier ALK inhibitor classes-including first-, second-, and third-generation agents-and it has shown activity against a range of treatment-emergent ALK mutations, such as the tough-to-treat G1202R substitution.2
The drug is engineered to cross the blood-brain barrier while avoiding activity against the closely related TRK receptor family. By bypassing TRK inhibition,neladalkib aims to reduce the CNS toxicities that have been associated with dual ALK/TRK inhibitors,while still enabling robust and lasting tumor control across multiple treatment settings.2
The ALKOVE-1 study is a global, open-label phase 1/2 trial evaluating neladalkib in p
Neladalkib Shows Promise in Advanced ALK-Positive NSCLC, Nuvalent Reports
Nuvalent, Inc. announced positive topline results from the pivotal ALKOVE-1 clinical trial evaluating neladalkib, an investigational selective tyrosine kinase inhibitor (TKI), in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with TKIs.
Key findings:
* Significant improvement in Progression-Free Survival (PFS): Neladalkib demonstrated a statistically significant and clinically meaningful improvement in PFS compared to crizotinib, a first-generation ALK TKI, in patients with TKI-resistant disease.
* Objective Response Rate (ORR): The ORR with neladalkib was also notably higher than that observed with crizotinib.
* Safety Profile: Neladalkib exhibited a manageable safety profile, consistent with prior clinical studies.
About Neladalkib and the ALKOVE-1 Trial:
neladalkib is designed to overcome resistance mutations commonly found in ALK-positive NSCLC patients who have progressed on first-line TKIs. The ALKOVE-1 trial (NCT05384626) is a global, randomized, Phase 3 trial comparing neladalkib to crizotinib in patients with ALK-positive NSCLC who have received prior ALK TKI therapy.
Implications:
These results suggest neladalkib has the potential to become a new treatment option for patients with advanced ALK-positive NSCLC who have developed resistance to existing TKIs. Nuvalent plans to discuss these findings with regulatory authorities and prepare for potential submissions.
Sources:
- ClinicalTrials.gov: ALKOVE-1
- Nuvalent announces positive topline pivotal data from ALKOVE-1 clinical trial of neladalkib for TKI pre-treated patients with advanced ALK-positive NSCLC. Nuvalent. November 17, 2025. Accessed November 17, 2025. https://investors.nuvalent.com/2025-11-17-Nuvalent-Announces-Positive-Topline-Pivotal-Data-from-ALKOVE-1-Clinical-Trial-of-Neladalkib-for-TKI-Pre-treated-Patients-with-Advanced-ALK-positive-NSCLC
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