NEW YORK – Nuvalent said on Monday it has started a Phase Ia/Ib trial evaluating its HER2 inhibitor NVL-330 in patients with HER2-amplified and -mutated non-small cell lung cancer.
The trial, dubbed HEROEX-1, will include patients who have already received treatment for advanced HER2-altered NSCLC, including those with HER2 exon 20 mutations, which are the most common HER2 mutations in this tumor type. Researchers will evaluate the overall safety and tolerability of NVL-330, determine the recommended Phase II dose, and evaluate preliminary anti-tumor activity.
Currently, there are no approved targeted therapies for HER2-altered NSCLC. "At the outset of our program, physician-scientists outlined the need for a HER2 therapy that maintained activity against HER2 exon 20 mutations, was selective for HER2 versus wild-type EGFR to limit gastrointestinal and skin toxicities associated with EGFR inhibition, and was brain penetrant to address and limit brain metastases," Nuvalent Chief Medical Officer Christopher Turner said in a statement. Preclinical data on NVL-330 suggest it has these characteristics and provided the rationale for testing it in the HEROEX-1 trial in patients with HER2-altered NSCLC, Turner added.
Nuvalent, based in Cambridge, Massachusetts, is also developing treatments for ROS1-mutant NSCLC and ALK-driven NSCLC. The firm began studying its lead candidate, zidesamtinib, in advanced NSCLC and other solid tumors with a ROS1 rearrangement in 2022. The firm is also evaluating an ALK inhibitor, NVL-655, in a Phase I/II trial in advanced ALK-positive NSCLC and other solid tumors.
Last year, Nuvalent raised $300 million in a public stock offering, which it said it would use to advance its three pipeline candidates.