Nuvalent disclosed that its investigational ALK‑selective inhibitor neladalkib achieved a 31% overall response rate (ORR) in 253 patients who had progressed on prior ALK tyrosine‑kinase inhibitors (TKIs). The response rate rose to 46% in the 63‑patient subset that had not previously received lorlatinib, and durable responses were seen in 76% of responders at 6 months, 64% at 12 months, and 53% at 18 months. Intracranial activity was notable, with a 32% intracranial ORR overall and 63% in patients with measurable CNS lesions, and a 13% intracranial complete‑response rate.
The exploratory cohort of 44 TKI‑naïve patients produced an 86% ORR and a 9% complete‑response rate. Durable responses were observed in 91% of responders at both 6‑ and 12‑month checkpoints, and intracranial activity was even more pronounced, with a 78% intracranial ORR and a 44% intracranial complete‑response rate in patients with measurable CNS disease.
These results address a critical unmet need in a heavily pre‑treated population that has limited options after lorlatinib. The data support a potential new therapeutic pathway that could improve outcomes for patients with CNS involvement, a setting where current ALK inhibitors have limited efficacy. The company’s Breakthrough Therapy Designation and planned pre‑New Drug Application meeting underscore the regulatory momentum behind the program.
Nuvalent’s leadership emphasized confidence in the data, noting that the Phase 3 ALKAZAR trial—comparing neladalkib to alectinib in TKI‑naïve patients—will further clarify the drug’s positioning in earlier lines of therapy. The company also highlighted its ongoing pipeline, including zidesamtinib for ROS1‑positive NSCLC, as part of its “OnTarget 2026” strategy.
Market reaction to the announcement was mixed. Investors weighed the encouraging efficacy data against the competitive landscape of established ALK inhibitors and the company’s cash runway needed to support the Phase 3 trial and potential commercialization. The mixed response reflects the typical volatility of clinical‑stage biopharma when pivotal data are released, but the overall sentiment remains positive given the drug’s strong activity profile and regulatory support.
Future outlook hinges on the outcomes of the Phase 3 trial and the company’s ability to secure regulatory approval. Successful completion of ALKAZAR and a favorable regulatory review could position neladalkib as a new standard of care in later lines of therapy, potentially expanding Nuvalent’s market share in the growing ALK‑TKI segment.
The content on BeyondSPX is for informational purposes only and should not be construed as financial or investment advice. We are not financial advisors. Consult with a qualified professional before making any investment decisions. Any actions you take based on information from this site are solely at your own risk.