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

NCT05118789 · tracked via the Priya Life Science UK tracker

Sponsor

Nuvalent Inc.

Phase

Phase 1/2

Started

2022-01-04

Last updated

2025-10-24

Condition(s) studied

Locally Advanced Solid TumorMetastatic Solid Tumor

Investigational drug(s) / intervention(s)

Zidesamtinib (NVL-520)

Zidesamtinib (NVL-520): Oral tablet of zidesamtinib (NVL-520)

Study 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.

Eligibility

Sex

ALL

Min age

12 Years

Max age

—

Healthy volunteers

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.

Primary outcome measure(s)

Maximum Tolerated Dose (MTD) (Phase 1) — Within 28 days of last patient dosed during dose escalation
Highest dose with dose-limiting toxicity (DLT) rate ≤ 25%
Recommended Phase 2 Dose (RP2D) — Within 28 days of last patient dosed during dose escalation.
To determine the RP2D
Objective Response Rate (ORR) (Phase 2) — 2-3 years after first patient dosed.
To determine ORR as assessed by BICR

Trial sites (63)

Facility	City	Region	Status
UCI Medical Center	Orange	California	Recruiting
Stanford Medicine	Palo Alto	California	Recruiting
UC Davis Comprehensive Cancer Center	Sacramento	California	Recruiting
University of Colorado Cancer Center	Denver	Colorado	Recruiting
Georgetown University Medical Center	Washington D.C.	District of Columbia	Recruiting
University of Miami	Coral Gables	Florida	Recruiting
University of Chicago	Chicago	Illinois	Recruiting
Mass General Hospital	Boston	Massachusetts	Recruiting
Dana-Farber Cancer Institute	Boston	Massachusetts	Recruiting
Henry Ford Cancer Institute	Detroit	Michigan	Recruiting
Washington University School of Medicine	St Louis	Missouri	Recruiting
NYU Langone Health	New York	New York	Recruiting
Memorial Sloan Kettering Cancer Center	New York	New York	Recruiting
Atrium Health Levine Cancer Institute	Charlotte	North Carolina	Recruiting
Ohio State University	Columbus	Ohio	Recruiting
Fox Chase Cancer Center	Philadelphia	Pennsylvania	Recruiting
Sarah Cannon Research Institute	Nashville	Tennessee	Recruiting
MD Anderson Cancer Center	Houston	Texas	Active Not Recruiting
NEXT Oncology - Virginia Cancer Specialists	Fairfax	Virginia	Recruiting
University of Washington / Fred Hutchinson Cancer Center	Seattle	Washington	Recruiting
Chris O'Brien Lifehouse	Camperdown	New South Wales	Recruiting
Peter MacCallum Cancer Centre	Melbourne	Victoria	Recruiting
University Hospital Leuven	Leuven	Belgium	Recruiting
Cross Cancer Institute	Edmonton	Alberta	Recruiting
Princess Margaret Cancer Research	Toronto	Ontario	Recruiting
Centre Legon Berard	Lyon	France	Recruiting
CHU de Nantes	Nantes	France	Recruiting
Claudius Regaud Institute	Toulouse	France	Recruiting
Institute Gustave Roussy	Villejuif	France	Recruiting
Cologne University Hospital	Cologne	Germany	Recruiting
Università Politecnica Marche	Ancona	Italy	Recruiting
IRCCS Istituto Tumori Giovanni Paolo II	Bari	Italy	Recruiting
Istituto Europeo di Oncologia	Milan	Italy	Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori	Milan	Italy	Recruiting
Istituto Oncologico Veneto	Padova	Italy	Recruiting
Ospedale Santa Maria delle Croci	Ravenna	Italy	Recruiting
Istituto Nazionale Tumori Regina Elena	Rome	Italy	Recruiting
Kanagawa Cancer Center	Kanagawa	Japan	Recruiting
Okayama University Hospital	Okayama	Japan	Recruiting
Kindai University Hospital	Osaka	Japan	Recruiting

+ 23 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05118789 on ClinicalTrials.gov ↗ ← All trials in the UK