Nuvalent, Inc. (NUVL) delivered some genuinely encouraging news on Monday from its ALKOVE-1 Phase 1/2 trial, testing its drug neladalkib in patients with advanced ALK-positive non-small cell lung cancer. This matters because these patients had already been through the wringer with prior treatments, and finding something that still works at that stage is no small feat.

The company locked in 150 mg once daily as the recommended Phase 2 dose during the trial's dose-escalation phase. The primary analysis looked at 253 patients who had already been treated with tyrosine kinase inhibitors—these weren't newly diagnosed folks. They'd been through a median of three prior lines of therapy, and more than half (51%) had already received chemotherapy. In other words, this was a heavily pretreated population where you'd expect diminishing returns.

Yet neladalkib still managed a 31% response rate across various subsets of these TKI-pretreated patients. Even better, the responses stuck around: 76% of those responses were still ongoing after six months, 64% after 12 months, and 53% after 18 months. The study hadn't even reached the median duration of response after 11.3 months of follow-up, suggesting some patients are experiencing sustained benefit.

The real eye-opener came from preliminary data on 44 treatment-naïve patients—people who hadn't received prior TKI therapy. This exploratory cohort from the Phase 2 portion of ALKOVE-1 showed an 86% preliminary objective response rate and a 9% complete response rate. Only two of the 38 responders had progressed so far. Duration of response ranged from 1.7+ to 14.8+ months, with response rates of 91% at both the 6-month and 12-month marks.

For patients with brain metastases—always a concern with lung cancer—the data looked solid too. Among 9 patients with measurable intracranial lesions, the intracranial objective response rate hit 78%, with a 44% complete response rate in the brain. The intracranial duration of response ranged from 3.1+ to 7.0+ months, and none of the responders experienced CNS progression.

Nuvalent is now enrolling treatment-naïve patients globally in ALKAZAR, a Phase 3 randomized controlled trial pitting neladalkib against alectinib head-to-head. The company also plans to sit down with the FDA at a pre-New Drug Application meeting to discuss the topline pivotal data for TKI-pretreated ALK-positive NSCLC patients.

Price Action: NUVL stock jumped 16.04% to $111.98 on Monday.