Nuvalent, Inc. (Nasdaq: NUVL), a US-based clinical-stage biopharmaceutical company, announced on Monday that it has started the phase two part of ALKOVE-1, its Phase 1/2 clinical trial of NVL-655 for subjects with ALK-positive non-small cell lung cancer (NSCLC) and other solid tumours, following alignment with the US Food and Drug Administration (FDA) on a recommended Phase two dose (RP2D) of 150mg once daily (QD).

NVL-655 is a novel brain-penetrant ALK-selective tyrosine kinase inhibitor (TKI) created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with inhibition of the structurally-related tropomyosin receptor kinase (TRK) family that may limit the use of currently available ALK TKIs.

In the Phase 1 portion of ALKOVE-1, six dose levels (15mg to 200mg QD) of NVL-655 were evaluated in heavily pre-treated patients with ALK-positive solid tumours, and a maximum tolerated dose was not reached. The RP2D of 150mg QD maintained steady state plasma levels above target efficacy thresholds (ALK wild type fusions and ALK single and compound mutations in both the periphery and in the CNS).

Darlene Noci, ALM, Nuvalent chief development officer, said, 'The transition of our NVL-655 program into Phase 2 advances a second, parallel opportunity towards our goal of bringing potential best-in-class therapies to patients as efficiently as possible. This sense of urgency is reflected in the thoughtful design of the Phase 2 portion of the ALKOVE-1 trial which aims to accelerate the clinical investigation that may support a potential marketing application towards an initial approval for previously treated patients with ALK-positive NSCLC. The Phase 2 portion also includes a TKI-naïve cohort which may provide an opportunity to generate early data, and could be conducted in parallel with a front-line registration-directed trial.'