Neladalkib NVL655

NVL-655 is currently in the clinical development phase. Phase 1 and 2 clinical trials have demonstrated robust efficacy in heavily pre-treated patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC). NVL-655 serves as a viable treatment option for patients who have previously received two or more lines of ALK TKI therapy—including first-, second-, and third-generation ALK inhibitors—and have subsequently developed resistance to these agents.

If a patient is currently taking a first-, second-, or third-generation ALK inhibitor and has not yet developed resistance, this product should not be purchased.

【Product Name】Nelderkib

【English Name】NVL-655

【Specification】50 mg × 28 capsules

【Manufacturer】Indar Pharmaceutical

NVL-655 was developed to overcome tumor resistance to first-, second-, and third-generation ALK inhibitors. Furthermore, the drug is designed to penetrate the Central Nervous System (CNS), thereby expanding treatment options for patients with brain metastases while avoiding the inhibition of the structurally similar TRK family of kinases.

In preclinical studies, NVL-655 demonstrated potent activity against ALK-driven cell lines, including those harboring single ALK mutations, complex mutations (two or more concurrent mutations), and EML4-ALK fusions. Additionally, the drug exhibits high selectivity by sparing other targets—such as TRK—and demonstrates a high level of brain penetration; preclinical data suggest its brain penetration is superior to that of Lorlatinib. Based on a preliminary assessment of study results, the FDA granted NVL-655 Breakthrough Therapy Designation in May 2024. This designation applies to patients who have previously received two or more lines of ALK TKI therapy.

【Indications】

For the treatment of patients with locally advanced or metastatic ALK-positive Non-Small Cell Lung Cancer (NSCLC).

NVL-655 is intended for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who have previously received two or more lines of ALK TKI therapy.

【Administration】

Take once daily; the dosage ranges from 50 mg to 150 mg per day.

At a dosage of 50 mg, NVL-655 achieves drug concentrations sufficient to inhibit brain metastases. Across a wide dose range, NVL-655 can completely eliminate ALK resistance mutations from patients' peripheral blood.

The median duration of treatment was 3.4 months; all patients who achieved a partial response continue to maintain stable disease, with the longest duration reaching one year.

Furthermore, among patients presenting with ALK resistance mutations at baseline, the objective response rate (ORR) was 65% (n = 11/17); among patients previously treated with lorlatinib (Lorbrena), the ORR was 41% (n = 12/29). The data also highlight the drug's activity within the central nervous system (CNS).

[Adverse Reactions]

Common treatment-related adverse events (TRAEs) observed in the trial included nausea (12%), elevated transaminases (12%), fatigue (9%), and constipation (7%). Grade 3 or higher TRAEs included elevated transaminases (n = 2), elevated creatine phosphokinase (n = 1), and fatigue (n = 1). At the time of analysis, the investigators had not yet determined the maximum tolerated dose.

[Product Specifications]

Product Name: NVL-655 / Neladalkib

Common Name: NVL-655

Composition: NVL-655

Dosage Form: Capsule

Specification: 50 mg × 28 capsules

Manufacturer: Indar Pharmaceutical

Indications: For the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC).

Dosage and Administration: Taken once daily; the dosage ranges from 50 mg to 150 mg per day.

At a dose of 50 mg, NVL-655 achieves drug concentrations sufficient to inhibit brain metastases.

Across a wide dose range, NVL-655 can completely eliminate ALK resistance mutations from patients' peripheral blood.