NCT05118789

A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)

A Phase 1/2 Study of the Highly Selective ROS1 Inhibitor Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors (ARROS-1)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 359 (estimated)
• Sponsor: Nuvalent Inc. · Industry
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of zidesamtinib (NVL-520), determine the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced ROS1-positive (ROS1+) NSCLC and other advanced ROS1-positive solid tumors. Phase 1 will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of zidesamtinib in patients with advanced ROS1-positive solid tumors. Phase 2 will determine the objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) of zidesamtinib at the RP2D. Secondary objectives will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR) of zidesamtinib in patients with advanced ROS1-positive NSCLC and other solid tumors.

Detailed description

In Phase 2, study patients will be enrolled into 5 distinct expansion cohorts: * Cohort 2a: ROS1-positive NSCLC naïve to Tyrosine Kinase Inhibitor (TKI) therapy and up to 1 prior chemotherapy and/or immunotherapy. * Cohort 2b: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy. * Cohort 2c: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy. * Cohort 2d: ROS1-positive NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy. * Cohort 2e: ROS1-positive solid tumor and progressed on any prior therapy.

Conditions

• Locally Advanced Solid Tumor
• Metastatic Solid Tumor

Interventions

Type	Name	Description
DRUG	Zidesamtinib (NVL-520)	Oral tablet of zidesamtinib (NVL-520)

Timeline

• Start date: 2022-01-04
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2021-11-12
• Last updated: 2025-10-24

Locations

63 sites across 14 countries: United States, Australia, Belgium, Canada, France, Germany, Italy, Japan, Netherlands, Singapore, South Korea, Spain, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study