CAMBRIDGE, Mass. — Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced that the first patient has been dosed in ALKAZAR, the company’s global Phase 3 randomized, controlled trial evaluating neladalkib for TKI-naïve patients with advanced ALK-positive non-small cell lung cancer (NSCLC), versus ALECENSA® (alectinib), a front-line standard of care.
“Neladalkib is rationally designed with the goal of addressing the combined medical needs of treating key drivers of disease progression such as brain metastases and treatment-emergent resistance mutations, while also offering a generally safe and well-tolerated safety profile supportive of long-term treatment,” said Darlene Noci, A.L.M., Chief Development Officer at Nuvalent. “We have been encouraged by neladalkib’s clinical profile to date, which we believe not only supports its potential to address clear medical needs for TKI pre-treated patients with advanced ALK-positive NSCLC, but also to translate to deep, durable responses for patients in the front-line setting. The initiation of the registration-directed ALKAZAR study enables us to explore this potential by comparing neladalkib to a front-line standard of care in a randomized, controlled clinical trial setting, and advances us towards our ultimate goal of bringing neladalkib to all patients with advanced ALK-positive NSCLC.”
The ALKAZAR trial is designed to enroll approximately 450 TKI-naïve patients with advanced ALK-positive NSCLC. Patients will be randomized 1:1 to receive neladalkib monotherapy or alectinib monotherapy, reflecting input from collaborating physician-scientists and alignment with global regulatory agencies. The primary endpoint is progression free survival (PFS) based on Blinded Independent Central Review (BICR). Secondary endpoints include overall survival, PFS based on investigator’s assessment, time to intracranial response, and BICR assessment of intracranial objective response rate (IC-ORR), intracranial duration of response (IC-DOR), objective response rate (ORR), duration of response (DOR), time to intracranial progression, and safety. Additional details can be found on www.clinicaltrials.gov (NCT06765109).
Neladalkib is also being evaluated in the Phase 2 portion of the ALKOVE-1 Phase 1/2 trial for TKI pre-treated patients with advanced ALK-positive NSCLC. Phase 1 data demonstrated that treatment with neladalkib resulted in durable clinical responses in heavily pre-treated patients. This included subgroups of patients who had likely exhausted all available therapies, including lorlatinib, had a history of brain metastases, and/or had single or compound ALK resistance mutations. Additionally, neladalkib demonstrated a generally safe and well-tolerated preliminary safety profile consistent with its ALK-selective, TRK-sparing design. The company expects to report topline pivotal data for TKI pre-treated patients with advanced ALK-positive NSCLC from the Phase 2 portion of ALKOVE-1 by year-end 2025.
“The currently available therapies represent important scientific advancements that provide hope for patients with ALK-positive NSCLC. However, these therapies have limitations that can lead to challenging treatment decisions for newly diagnosed patients and their health care providers,” said Kirk Smith, President of the Board of ALK Positive Inc. “We encourage continued innovation and the investigation of new treatment opportunities for all patients with ALK-positive NSCLC and look forward to following the progress of the ALKAZAR study.”
About Neladalkib
Neladalkib is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.
About Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, and multiple discovery-stage research programs.
Investor Contact
Chelcie Lister – Nuvalent, Inc.,