Nuvalent says preliminary Phase 1 ALKOVE-1 trial data demonstrates activity

Nuvalent announced preliminary data from the Phase 1 dose-escalation portion of its ongoing ALKOVE-1 Phase 1/2 clinical trial of NVL-655 for patients with advanced ALK-positive non-small cell lung cancer, NSCLC, and other solid tumors as reported in an abstract accepted for presentation at the 35th AACR-NCI-EORTC, or ANE, Symposium in Boston, Massachusetts. Updated preliminary data will be presented at the conference and during a live webcast and conference call with management on October 13 at 8:00am ET. 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 adverse events associated with tropomyosin receptor kinase, TRK, inhibition that may limit the use of currently available ALK TKIs. NVL-655 is currently being evaluated in the ALKOVE-1 Phase 1/2 clinical trial, a first-in-human study of NVL-655 in patients with advanced ALK-positive NSCLC and other solid tumors. Preliminary activity of NVL-655 was demonstrated in this heavily pre-treated patient population as measured by objective response rate per RECIST 1.1. Partial responses were observed in 45% of response-evaluable patients with ALK-positive NSCLC who received NVL-655 at doses ranging from 15-150 mg once daily. An ORR of 65% was observed in patients with baseline ALK resistance mutations, and an ORR of 41% was observed in patients post-lorlatinib, including cases with compound resistance mutations. Early indicators of CNS activity were also observed. Preliminary pharmacokinetic analysis demonstrated dose-proportional exposure, and preliminary pharmacodynamic analysis showed reductions, including clearance, of ALK fusion and mutation variants in ctDNA. NVL-655 was well-tolerated and treatment-related adverse events were generally mild. “We are strongly encouraged by these preliminary safety and clinical activity data from the Phase 1 portion of our ALKOVE-1 clinical trial, which demonstrate the potential for NVL-655 to achieve its target product profile of potent and selective targeting of ALK fusions and secondary ALK single and compound resistance mutations, brain penetrance, and the avoidance of TRK inhibition,” said Christopher Turner, M.D., Chief Medical Officer of Nuvalent. “We look forward to presenting an update to this data at the AACR-NCI-EORTC Symposium later this month.”