A recent publication in the scientific journal Frontiers in Medicine sets out detailed, updated results from the ALKOVE-1 clinical study. This phase 1/2 study is investigating neladalkib, a fourth-generation tyrosine kinase inhibitor (TKI), in patients with advanced solid tumours carrying an ALK fusion, primarily non-small cell lung cancer (NSCLC).
Why does this research matter so much?
For many ALK+ patients, the treatment pathway often begins with alectinib or brigatinib, followed by lorlatinib as the disease progresses. Over time, however, the cancer develops complex resistance, such as the G1202R mutation or compound mutations. The ALKOVE-1 study set out to show that neladalkib can not only overcome this resistance, but do so in a more targeted way.
The key points from the publication
- Activity against resistance mutations: neladalkib showed notable activity against the G1202R mutation, with an objective response rate (ORR) of 71% in patients with this specific mutation.
- Selectivity and safety: a major success of this medicine is its ability to target ALK while sparing the TRK receptors in the brain. This leads to a considerable reduction in neurological side effects (such as problems with memory, mood or speech) that are often seen with lorlatinib.
- Activity in the brain: the data confirm that neladalkib penetrates the central nervous system very well. In patients with measurable brain metastases, the intracranial response rate was 63%.
- TKI-naïve patients: although neladalkib is often tested as a later-line option, results in patients who have never received a TKI are impressive, with a response rate of 86%.
An encouraging tolerability profile
The article emphasises that most side effects are mild to moderate in nature. Raised liver enzymes remain the most common adverse effect, but these are generally manageable through dose adjustment or a brief interruption of treatment.
What does this mean for the future?
On the strength of these results, neladalkib has been granted “Breakthrough Therapy” designation by the FDA. In Belgium we await official approval by the EMA; in the meantime, the phase 3 ALKAZAR study continues to recruit patients in order to compare this medicine directly with current standard first-line treatments.
This publication confirms that neladalkib is a serious candidate to become a standard therapeutic option, potentially offering longer disease control and better quality of life for ALK-positive patients.
Read the full scientific article on the Frontiers in Medicine website via this link: View the original article.