Nuvalent’s stock price oscillated after it’s investigational ALK-selective inhibitor showed promise in patients with advanced ALK-positive non-small cell lung cancer (NSCLC).
In the Phase I/II ALKOVE-1 study (NCT05384626), neladalkib was associated with a 31% overall response rate (ORR) amongst patients who had previously received prior treatment with any anaplastic lymphoma kinase tyrosine kinase inhibitor (ALK TKI) and/or chemotherapy.
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In this patient population, there was a 76% duration of response (DOR) at six months. This reduced to 64% at 12 months and 53% at 18 months.
Median DOR (mDOR) for the full patient population has not yet been reached, with median follow-up of 11.3 months.
In this primary analysis population, 78% of patients had received two or more prior ALK TKIs, with some also receivingprior chemotherapy, with 91% of these having received prior treatment with Pfizer’s Lorbrena (lorlatinib).
After the data was released, Nuvalent’s stock initially dropped by 2.88% to $93.72 at market open on 17 November, compared to the 14 November market close of $96.50. The stock price then quickly gained momentum and increased significantly throughout the day, closing at $108.00. Immediately after market close, Nuvalent announced a public offering of $500m of shares.
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By GlobalDataFurther analysis of the data in patients who had a G1202R mutation, a change within the ALK gene, where the where amino acid glycine is replaced by arginine at position 1202, saw a 68% ORR, with a six-month DOR of 84%, which reduced to 70% after 18 months.
In analysis of an earlier stage subpopulation of patients who had received at least one previous ALK TKI and chemotherapy but were Lorbrena naïve, there was a 46% ORR, with an 89% DOR at six months, reducing to 60% after 18 months.
The most frequent treatment-emergent adverse events (TEAEs) that occurred in at least 15% of patients were increased alanine aminotransferase, increased aspartate aminotransferase, constipation, dysgeusia, peripheral oedema, cough and nausea.
On the back of this data, Nuvalent plans to discuss the top line pivotal data for TKI pre-treated ALK-positive NSCLC with the US Food and Drug Administration (FDA) at a pre-new drug application (NDA) meeting.
Nuvalent CEO Dr James Porter said: “Our focus remains on delivering our precisely targeted therapies to patients as quickly as possible, and we look forward to discussing these pivotal data with the FDA and aligning on a potential registration path for neladalkib in TKI pre-treated patients with advanced ALK-positive NSCLC.”
Nuvalent also eyeing TKI-naïve population
Nuvalent’s drug is also being investigated in the Phase III ALKAZAR trial (NCT06765109) in TKI-naïve patients with advanced ALK-positive NSCLC, in which neladalkib is being pitted against Chugai Pharmaceutical’s Alecensa (alectinib), the current standard of care
Data from an exploratory, TKI-naïve cohort of 44 patients in the Phase I/II ALKOVE-1 trial reported an ORR of 86% and a complete response (CR) rate of 9% in patients treated with neladalkib. Following this data cutoff, two of the 38 responders have since seen disease progression.
If approved, a patient-based forecast by GlobalData predicts the drug will make $580m in sales in 2032.
Another potential player in the ALK-positive NSCLC space is Xcovery and Betta Pharmaceuticals’ TKI Ensacove (ensartinib). In data presented at the 2025 European Society of Medical Oncology (ESMO) Congress, held on 17-21 October in Berlin, Germany, disease-free survival (DFS) was reached in 86.4% of patients treated with ensartinib, compared to 53.5% in the placebo control arm in the Phase III ELEVATE trial.
According to GlobalData’s analyst consensus forecast, the global market for kinase inhibitors targeting ALK-mutated NSCLC is expected to reach $5.7bn by 2031.
GlobalData valued the full NSCLC market in the seven major markets (7MM: US, France, Germany, Italy, Spain, the UK, and Japan) at $24.1bn in 2022 and expects the market to reach $56.5bn by 2032.
GlobalData is the parent company of Clinical Trials Arena.
