Nuvalent Initiates Phase 3 Trial for Neladalkib in TKI-Naïve ALK-Positive NSCLC

Nuvalent has initiated a Phase 3 trial, ALKAZAR, evaluating neladalkib for TKI-naïve patients with advanced ALK-positive non-small cell lung cancer (NSCLC) versus ALECENSA. The trial aims to enroll approximately 450 patients and will compare progression-free survival based on Blinded Independent Central Review. Neladalkib is also being evaluated in the Phase 2 portion of the ALKOVE-1 trial for TKI pre-treated patients with advanced ALK-positive NSCLC, with topline data expected by year-end 2025.

Nuvalent, Inc. (Nasdaq: NUVL) has announced the initiation of the ALKAZAR Phase 3 randomized controlled trial, evaluating neladalkib for TKI-naïve patients with advanced ALK-positive non-small cell lung cancer (NSCLC). The trial aims to enroll approximately 450 patients and will compare neladalkib against ALECENSA® (alectinib), a current front-line standard treatment. The primary endpoint is progression-free survival (PFS) based on Blinded Independent Central Review (BICR), with multiple secondary endpoints including overall survival and intracranial response measures.

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 durable clinical responses in heavily pre-treated patients, including those with brain metastases and resistance mutations. Topline data from the Phase 2 portion of ALKOVE-1 is expected by year-end 2025.

The ALKAZAR trial is designed to enroll TKI-naïve patients with advanced ALK-positive NSCLC, with patients randomized 1:1 to receive neladalkib monotherapy or alectinib monotherapy. The study is aligned with global regulatory agencies and reflects input from collaborating physician-scientists. The primary endpoint is PFS based on BICR, with secondary endpoints including 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.

Neladalkib is a novel brain-penetrant ALK-selective inhibitor designed to overcome limitations observed with currently available ALK inhibitors. It 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. Neladalkib also aims to improve treatment options for patients with brain metastases and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family.

Nuvalent is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer. The company's pipeline includes investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, and multiple discovery-stage research programs.

References:
[1] https://www.prnewswire.com/news-releases/nuvalent-announces-initiation-of-alkazar-phase-3-randomized-controlled-trial-evaluating-neladalkib-for-patients-with-tki-naive-alk-positive-nsclc-302508977.html
[2] https://www.stocktitan.net/news/NUVL/nuvalent-announces-initiation-of-alkazar-phase-3-randomized-qedhm14yzz3x.html