Nuvalent Launches Phase 2 ALKOVE-1 Trial for ALK-Positive NSCLC and Solid Tumors

Nuvalent, a biopharmaceutical firm, has advanced its drug candidate NVL-655 into Phase 2 of the ALKOVE-1 clinical trial. The trial is designed for patients with ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors, following the FDA's approval of a 150 mg once-daily dose. This new ALK-selective tyrosine kinase inhibitor is intended to tackle resistance to treatment, brain metastases, and adverse CNS events linked to TRK inhibition, which are challenges associated with existing ALK inhibitors.

During Phase 1, various doses of NVL-655 were tested on patients with ALK-positive tumors who had prior treatments, without reaching a maximum tolerated dose. The selected dose of 150 mg showed consistent plasma levels above the efficacy targets for ALK mutations and maintained a good safety profile.

Darlene Noci, Chief Development Officer at Nuvalent, emphasized the importance of the Phase 2 trial's design, which is intended to expedite clinical investigation for a potential marketing application for patients with ALK-positive NSCLC who have had prior TKI treatments. The trial will also include a cohort of TKI-naïve patients to gather preliminary data.

James Porter, CEO of Nuvalent, highlighted the significance of this advancement as part of the company's OnTarget 2026 plan, aiming to deliver targeted therapies to cancer patients. The company's strategy with NVL-655 is to not only meet the needs of later-line patients but also to innovate treatment paradigms.

The Phase 2 trial will take place globally and will assess NVL-655's efficacy in several patient groups, including those pre-treated with TKIs and those who are TKI-naïve. The trial's design accommodates patients with various stages of NSCLC and other solid tumors harboring ALK rearrangements or mutations.

The FDA's support for the 150 mg once-daily dose was based on Phase 1 data, which indicated that NVL-655 could be a leading therapy for ALK-positive NSCLC. The drug's selection as a potential best-in-class therapy was due to its ability to maintain plasma levels above efficacy thresholds, its favorable tolerability, and the early anti-tumor activity observed across different doses.

NVL-655 is unique in its design to overcome resistance to previous ALK inhibitors and is capable of penetrating the CNS, which could improve treatment for patients with brain metastases. The drug has received orphan drug status for ALK-positive NSCLC and is part of Nuvalent's broader pipeline targeting various cancer types.

Nuvalent is working towards several milestones in 2024 as outlined in the OnTarget 2026 plan, including progressing the ARROS-1 trial for another drug candidate NVL-520 and initiating the HER2 program's Phase 1 trial. The company's mission is to develop innovative small molecules that can overcome resistance, minimize side effects, and provide more durable responses for cancer patients.