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

RecruitingPhase 1/2

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)

Who can join

Ages 12 and older · All sexes

Full eligibility criteria
Inclusion Criteria:

1. Age ≥18 years (Cohort 2e only: Age ≥12 years).
2. Disease Criteria:

   1. Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement.
   2. Phase 2: Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement.
   3. Phase 2: Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement.
3. Prior anticancer treatment (except cohort 2a).
4. Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1. Phase 2: Must have measurable disease according to RECIST 1.1.
5. Adequate baseline organ function and bone marrow reserve.

Exclusion Criteria:

1. Patient's cancer has a known oncogenic driver alteration other than ROS1.
2. Known allergy/hypersensitivity to excipients of NVL-520.
3. Major surgery within 4 weeks of first dose of study drug.
4. Ongoing anticancer therapy.
5. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.

About the study

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.

What is being tested

Sponsor: Nuvalent Inc. · Participants: 359 · Started: Jan 4, 2022

Contact the study team

Official record on ClinicalTrials.gov — NCT05118789

Locations in the U.S.

CaliforniaUCI Medical Center, Orange
Stanford Medicine, Palo Alto
UC Davis Comprehensive Cancer Center, Sacramento
ColoradoUniversity of Colorado Cancer Center, Denver
District of ColumbiaGeorgetown University Medical Center, Washington D.C.
FloridaUniversity of Miami, Coral Gables
IllinoisUniversity of Chicago, Chicago
MassachusettsDana-Farber Cancer Institute, Boston
Mass General Hospital, Boston
MichiganHenry Ford Cancer Institute, Detroit
MissouriWashington University School of Medicine, St Louis
New YorkMemorial Sloan Kettering Cancer Center, New York
NYU Langone Health, New York
North CarolinaAtrium Health Levine Cancer Institute, Charlotte
OhioOhio State University, Columbus
PennsylvaniaFox Chase Cancer Center, Philadelphia
TennesseeSarah Cannon Research Institute, Nashville
VirginiaNEXT Oncology - Virginia Cancer Specialists, Fairfax
WashingtonUniversity of Washington / Fred Hutchinson Cancer Center, Seattle

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.