On October 18, 2025 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported preliminary data from the ongoing ALKOVE-1 Phase 1/2 clinical trial of neladalkib, an investigational ALK-selective inhibitor, in patients with advanced ALK-positive solid tumors outside of non-small cell lung cancer (NSCLC). These data will be presented during a poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025, taking place October 17-21, 2025, in Berlin, Germany, and are available on Nuvalent’s website at www.nuvalent.com.

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"Neladalkib was designed with the goal of being a best-in-class ALK-selective inhibitor, and initial clinical safety and efficacy data have been reported in TKI pre-treated ALK-positive NSCLC with topline pivotal data expected by the end of this year. Today, we’re excited to share the first report of neladalkib’s encouraging preliminary activity beyond NSCLC, which continue to demonstrate its target characteristics of activity against ALK and ALK resistance mutations, brain penetrance, and avoidance of TRK inhibition associated with off-target CNS adverse events," saidChristopher Turner, M.D., Chief Medical Officer of Nuvalent. "These data highlight the potential for an ALK-selective inhibitor to broadly address medical needs for patients with ALK-positive solid tumors, and the importance of widespread genomic testing. We continue to enroll adult and adolescent TKI naïve and TKI pre-treated patients with advanced ALK-positive solid tumors beyond NSCLC in the global Phase 2 portion of our ALKOVE-1 study, and look forward to providing additional updates as these data mature."

Preliminary data are reported for 34 response-evaluable patients enrolled across 14 solid tumor types outside of NSCLC in the Phase 1 and Phase 2 portions of the ALKOVE-1 clinical trial as of a data cutoff date of August 7, 2025. The majority (32/34) of patients received the recommended Phase 2 dose of 150 mg once daily. Patients were ALK TKI-naïve (38%, 13/34) or ALK TKI pre-treated (62%, 21/34), and 62% (21/34) of patients had received prior chemotherapy.

Among all patients with advanced ALK-positive solid tumors treated with neladalkib, an objective response rate of 44% (15/34) was observed, including 9/13 patients who were ALK TKI-naïve and 6/21 who were ALK TKI pre-treated. 80% (12/15) of responders remained on treatment without disease progression as of the data cutoff date. Three case studies support neladalkib’s potential to induce deep and durable responses in a range of treatment settings:

Treatment ongoing for approximately 12 months with partial response in a TKI-naïve patient with an inflammatory myofibroblastic tumor previously treated with standard of care chemotherapy;
Treatment ongoing for approximately 16 months with partial response in a TKI and chemotherapy pre-treated patient with peritoneal mesothelioma; and,
Treatment ongoing for approximately 10 months with confirmed intracranial complete response in a TKI pre-treated patient with adenocarcinoma of unknown origin with baseline brain metastasis and ALK V1180L resistance mutation.
Among these 34 patients, neladalkib was generally well-tolerated with low rates of dose reduction (8.8%) and no discontinuations due to treatment-related adverse events as of the data cutoff date. The preliminary overall safety profile was consistent with its ALK-selective, TRK-sparing design, and with previously reported data.

Enrollment is ongoing in the global Phase 2 cohort of the ALKOVE-1 trial for adult and adolescent patients with advanced ALK-positive solid tumors other than NSCLC.

The company remains on track to report topline data for patients with TKI pre-treated ALK-positive NSCLC from the ALKOVE-1 trial by the end of 2025. Neladalkib is also being evaluated in ALKAZAR, a global Phase 3 randomized, controlled trial for the treatment of patients with TKI-naïve ALK-positive NSCLC.

About Neladalkib

Neladalkib is an investigational brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.

(Press release, Nuvalent, OCT 18, 2025, View Source [SID1234656748])