Recruiting

Phase 1

Phase 2

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

Sponsor:

Nuvalent Inc.

Code:

NCT05118789

Conditions

Locally Advanced Solid Tumor

Metastatic Solid Tumor

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Interventions

Zidesamtinib (NVL-520)

Study Details

Brief 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.

Conditions

Locally Advanced Solid Tumor

Metastatic Solid Tumor

Study ID

NCT05118789

Start date

Jan 4, 2022

Status verified date

Jul, 2025

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

359 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1 dose escalation

Zidesamtinib (NVL-520) oral daily dosing

experimental: Cohort 2a

ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy

experimental: Cohort 2b

ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy

experimental: Cohort 2c

ROS1+ NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy

experimental: Cohort 2d

ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy

experimental: Cohort 2e

ROS1+ solid tumor and progressed on any prior therapy

Interventions

Zidesamtinib (NVL-520)

Oral tablet of zidesamtinib (NVL-520)

Primary outcome measure

Maximum Tolerated Dose (MTD) (Phase 1) [ Time Frame: Within 28 days of last patient dosed during dose escalation ]
Recommended Phase 2 Dose (RP2D) [ Time Frame: Within 28 days of last patient dosed during dose escalation. ]
Objective Response Rate (ORR) (Phase 2) [ Time Frame: 2-3 years after first patient dosed. ]

Central Contacts and Locations

Central contacts

Nuvalent

857-357-7000 clinicaltrials@nuvalent.com

Locations

UCI Medical Center

Recruiting

Orange, California, United States, 92868

Principal Investigator:

Misako Nagasaka, MD, PhD

Stanford Medicine

Recruiting

Palo Alto, California, United States, 94305

Principal Investigator:

Joel Neal, MD, PhD

UC Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Principal Investigator:

Jonathan Riess, MD

University of Colorado Cancer Center

Recruiting

Denver, Colorado, United States, 80045

Principal Investigator:

Ross Camidge, MD

Georgetown University Medical Center

Recruiting

Washington D.C., District of Columbia, United States, 20007

Principal Investigator:

Stephen Liu, MD

University of Miami

Recruiting

Coral Gables, Florida, United States, 33146

Principal Investigator:

Gilberto de Lima Lopes, MD

University of Chicago

Recruiting

Chicago, Illinois, United States, 60637

Principal Investigator:

Marina Garassino, MD

Mass General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator:

Jessica Lin, MD

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator:

Alice Shaw, MD, PhD

Henry Ford Cancer Institute

Recruiting

Detroit, Michigan, United States, 48202

Principal Investigator:

Shirish Gadgeel, MD

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Principal Investigator:

Saiama Waqar, MD

NYU Langone Health

Recruiting

New York, New York, United States, 10016

Principal Investigator:

Elaine Shum, MD

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Alexander Drilon, MD

Atrium Health Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28204

Principal Investigator:

Daniel Haggstrom, MD

Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator:

Dwight Owen, MD, MS

Fox Chase Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19111

Principal Investigator:

Jessica Bauman, MD

Sarah Cannon Research Institute

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

Melissa Johnson, MD

NEXT Oncology - Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

Principal Investigator:

Alexander Spira, MD, PhD

University of Washington / Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Principal Investigator:

Christina Baik, MD, MPH

Cross Cancer Institute

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Principal Investigator:

Quincy Chu, MD

Princess Margaret Cancer Research

Recruiting

Toronto, Ontario, Canada, M5GG 1L7

Principal Investigator:

Geoffrey Liu, MD

More Information

Sponsor

Nuvalent Inc.

Last update posted

Oct 24, 2025

Last verified

Jul, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Nuvalent Inc. on 2025-10-24.