Nuvalent’s Neladalkib Delivers Pivotal ALKOVE-1 Data in ALK-positive Lung Cancer
- 3 days ago
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Nuvalent, Inc., a clinical-stage biotech, has recently sent shockwaves through the oncology market by announcing positive topline pivotal data from its ALKOVE-1 trial. These results strongly suggest that the investigational ALK-selective inhibitor, neladalkib, could become a new, crucial treatment option for patients battling advanced ALK-positive non-small cell lung cancer (NSCLC).
The successful phase 1/2 trial data positions Nuvalent to seek regulatory discussion with the FDA soon, potentially setting up neladalkib as a significant challenger to established drugs like Pfizer’s Lorbrena.
The ALKOVE-1 trial enrolled patients with advanced ALK-positive NSCLC who had previously received tyrosine kinase inhibitor (TKI) treatment. Currently, these patients typically start on Roche’s Alecensa, progress to Pfizer’s Lorbrena, and then often face few third-line treatment options. Neladalkib was specifically designed to overcome the resistance and safety issues often associated with existing TKIs and is intended to work across any line of therapy.
In the study’s primary analysis population, which included 253 TKI pre-treated patients, neladalkib demonstrated an objective response rate (ORR) of 31%. This cohort was heavily pre-treated, with patients having received a median of three prior lines of therapy. Critically, the drug showed significant durability: 76% of responses were ongoing after six months, falling to 64% at 12 months and 53% at 18 months. The median duration of response (DOR) was yet to be reached after 11.3 months of follow-up.
For patients who had not previously received Lorbrena (a subgroup of 63 patients), the ORR was higher at 46%, with 80% of responses lasting at least 12 months. Analysts have noted that Lorbrena previously won approval for post-Alecensa use based on an approximate 40% response rate and a DOR of about seven months. Nuvalent executives believe neladalkib will drive “more prolonged durability” compared to Lorbrena on cross-trial comparison, aiming to be "meaningfully better".
Furthermore, neladalkib showed potent efficacy against the difficult-to-treat G1202R mutation, a key driver of disease progression, achieving a 68% response rate in that specific population. Intracranial responses were also observed in patients with brain metastases.
Regarding safety, neladalkib demonstrated a generally well-tolerated profile. The most frequent treatment-emergent adverse events (TEAEs) included increases in two liver enzymes, which were seen in 44% and 47% of patients. Importantly, only 5% of patients discontinued treatment due to adverse events.
Nuvalent plans to discuss these robust findings with the FDA at a pre-New Drug Application meeting. While the initial target population is the TKI-pretreated group, Nuvalent is simultaneously running a Phase 3 trial pitting neladalkib against Alecensa to establish its use in TKI-naïve patients. Preliminary data from an exploratory cohort of 44 TKI-naïve patients showed an impressive 86% response rate.
These positive results underscore the company’s ongoing progress in its cancer drug programs, which also includes its ROS1 inhibitor, zidesamtinib.
The positive pivotal data from the ALKOVE-1 trial acts like a key turning point in a challenging race; where existing treatments are like reliable but slower vehicles, Neladalkib is entering the track hoping to be a faster, more fuel-efficient design, potentially setting a new standard for durability against a highly resistant opponent.
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Keywords: ALK-positive Lung Cancer
ALK-positive Lung Cancer
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