Nuvalent reveals promising ALK inhibitor NVL-655 in cancer study

Nuvalent, Inc. has published a manuscript in Cancer Discovery detailing the design and characterization of NVL-655, an ALK-selective inhibitor. This publication highlights the preclinical activity of NVL-655 and includes preliminary clinical case studies from the ongoing ALKOVE-1 Phase 1/2 trial, which targets patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors. The study emphasizes NVL-655's potential to overcome limitations of existing ALK tyrosine kinase inhibitors (TKIs), such as treatment-emergent resistance and adverse neurological effects. The manuscript presents three case studies of patients with ALK fusion-positive lung cancers who had previously received various ALK TKIs, including lorlatinib, and exhibited brain metastases or ALK G1202R mutations. Notably, NVL-655 demonstrated tumor responses in these patients without causing central nervous system (CNS) side effects typically associated with off-target TRK inhibition. This suggests that NVL-655 may provide a safer and more effective treatment option for this patient population. Enrollment for the global Phase 2 portion of the ALKOVE-1 trial is ongoing, with the intent to gather data that could support regulatory approval. Updated results from the Phase 1 portion are set to be presented at the European Society for Medical Oncology (ESMO) Congress 2024. The trial aims to evaluate NVL-655's efficacy in patients who have developed resistance to prior ALK inhibitors, highlighting its design for CNS penetrance and avoidance of TRK-related adverse events. The publication serves as a significant step in Nuvalent's strategy to advance targeted therapies for ALK-positive NSCLC, addressing critical unmet needs in the treatment landscape. The findings underscore the importance of continued research and development in this area, as well as the potential for NVL-655 to improve outcomes for patients facing challenging treatment scenarios.