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

NCT05118789 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NVL-520-01
• Study Type: interventional
• Target: 359
• Locations: 14 countries
• Sites: 63

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

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) (Phase 1)

  Highest dose with dose-limiting toxicity (DLT) rate ≤ 25%

  Within 28 days of last patient dosed during dose escalation

• Recommended Phase 2 Dose (RP2D)

  To determine the RP2D

  Within 28 days of last patient dosed during dose escalation.

• Objective Response Rate (ORR) (Phase 2)

  To determine ORR as assessed by BICR

  2-3 years after first patient dosed.

Secondary Outcomes (21)

• Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0

  Approximately 3 years.

• Maximum plasma concentration (Cmax) of NVL-520

  Pre-dose and up to 24 hours post-dose

• Plasma concentration at the end of the dosing interval (Ctau) of NVL-520

  Pre-dose and up to 24 hours post-dose

• Average plasma concentration (Cavg) of NVL-520

  Pre-dose and up to 24 hours post-dose

• Time of maximum concentration (Tmax) of NVL-520

  Pre-dose and up to 24 hours post-dose

Study Arms (6)

Phase 1 dose escalation

EXPERIMENTAL

Zidesamtinib (NVL-520) oral daily dosing

Drug: Zidesamtinib (NVL-520)

Cohort 2a

EXPERIMENTAL

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

Drug: Zidesamtinib (NVL-520)

Cohort 2b

EXPERIMENTAL

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

Drug: Zidesamtinib (NVL-520)

Cohort 2c

EXPERIMENTAL

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

Drug: Zidesamtinib (NVL-520)

Cohort 2d

EXPERIMENTAL

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

Drug: Zidesamtinib (NVL-520)

Cohort 2e

EXPERIMENTAL

ROS1+ solid tumor and progressed on any prior therapy

Drug: Zidesamtinib (NVL-520)

Interventions

Zidesamtinib (NVL-520) DRUG

Oral tablet of zidesamtinib (NVL-520)

Cohort 2a; Cohort 2b; Cohort 2c; Cohort 2d; Cohort 2e; Phase 1 dose escalation

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years (Cohort 2e only: Age ≥12 years).
• Disease Criteria:
• Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement.
• Phase 2: Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement.
• Phase 2: Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement.
• Prior anticancer treatment (except cohort 2a).
• 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.
• Adequate baseline organ function and bone marrow reserve.

You may not qualify if:

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

Sponsors & Collaborators

• Nuvalent Inc.: lead

Study Sites (63)

UCI Medical Center

Orange, California, 92868, United States

RECRUITING

Stanford Medicine

Palo Alto, California, 94305, United States

RECRUITING

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

University of Colorado Cancer Center

Denver, Colorado, 80045, United States

RECRUITING

Georgetown University Medical Center

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

RECRUITING

University of Miami

Coral Gables, Florida, 33146, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Mass General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Atrium Health Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

NEXT Oncology - Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

University of Washington / Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

University Hospital Leuven

Leuven, 3000, Belgium

RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

Princess Margaret Cancer Research

Toronto, Ontario, M5GG 1L7, Canada

RECRUITING

Centre Legon Berard

Lyon, 69008, France

RECRUITING

CHU de Nantes

Nantes, 44000, France

RECRUITING

Claudius Regaud Institute

Toulouse, 31300, France

RECRUITING

Institute Gustave Roussy

Villejuif, 94805, France

RECRUITING

Cologne University Hospital

Cologne, Germany

RECRUITING

Università Politecnica Marche

Ancona, 60121, Italy

RECRUITING

IRCCS Istituto Tumori Giovanni Paolo II

Bari, 70124, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Istituto Oncologico Veneto

Padua, 35128, Italy

RECRUITING

Ospedale Santa Maria delle Croci

Ravenna, 48121, Italy

RECRUITING

Istituto Nazionale Tumori Regina Elena

Rome, 00128, Italy

RECRUITING

Kanagawa Cancer Center

Kanagawa, 241-8515, Japan

RECRUITING

Okayama University Hospital

Okayama, 700-8558, Japan

RECRUITING

Kindai University Hospital

Osaka, 577-8502, Japan

RECRUITING

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, 104-0045, Japan

RECRUITING

The Cancer Institute Hospital Of JFCR

Tokyo, 135-8550, Japan

RECRUITING

Wakayama Medical University Hospital

Wakayama, 641-8510, Japan

RECRUITING

Netherlands Cancer Institute

Amsterdam, 1066, Netherlands

RECRUITING

University Medical Centre Groningen

Groningen, Netherlands

RECRUITING

National University Hospital Singapore

Singapore, 119074, Singapore

RECRUITING

National Cancer Centre Singapore

Singapore, 168583, Singapore

RECRUITING

National Cancer Center

Gyeonggi-do, 10408, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

University Hospital of A Coruña

A Coruña, 15006, Spain

RECRUITING

UOMI Cancer Center - Clinica Tres Torres

Barcelona, 08017, Spain

RECRUITING

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

RECRUITING

Gregorio Marañón Hospital

Madrid, 28007, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

RECRUITING

Chung Shan Medical University Hospital

Taichung, 40201, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

RECRUITING

Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vivek Upadhyay, MD, MBI

  Nuvalent Inc.

  STUDY DIRECTOR

Central Study Contacts

Nuvalent

CONTACT

857-357-7000; clinicaltrials@nuvalent.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2021
• First Posted: November 12, 2021
• Study Start: January 4, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 24, 2025

Record last verified: 2025-07

Locations

NL (2); AU (2); SG (2); ES (6); GB (2); IT (7); US (20); CA (2); KR (4); TW (3); FR (4); BE (1); DE (1); JP (7)