Locally Advanced Solid TumorPhase 1/2NCT05118789
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 testing Zidesamtinib (NVL-520) in people with Locally Advanced Solid Tumor and Metastatic Solid Tumor, run by Nuvalent Inc. at 63 sites in 14 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Locally Advanced Solid Tumor, Metastatic Solid Tumor
- What is being tested?
- Zidesamtinib (NVL-520)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 359 participants
- Where
- 63 sitesin 14 countries
- Study dates
- 4 Jan 2022to 31 Dec 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
63 sites in 14 countries. Contact the study team or a site near you to ask about taking part.
63 sites in 14 countries
United States20 sites, 19 recruiting
- Recruiting
Mass General Hospital
Boston, Massachusetts, 02114
Jessica Lin, MD
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Alice Shaw, MD, PhD
- Recruiting
Atrium Health Levine Cancer Institute
Charlotte, North Carolina, 28204
Daniel Haggstrom, MD
- Recruiting
University of Chicago
Chicago, Illinois, 60637
Marina Garassino, MD
- Recruiting
Ohio State University
Columbus, Ohio, 43210
Dwight Owen, MD, MS
- Recruiting
University of Miami
Coral Gables, Florida, 33146
Gilberto de Lima Lopes, MD
- Recruiting
University of Colorado Cancer Center
Denver, Colorado, 80045
Ross Camidge, MD
- Recruiting
Henry Ford Cancer Institute
Detroit, Michigan, 48202
Bindu Potugari, MD
- Recruiting
NEXT Oncology - Virginia Cancer Specialists
Fairfax, Virginia, 22031
Alexander Spira, MD, PhD
- Active, not recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Melissa Johnson, MD
- Recruiting
NYU Langone Health
New York, New York, 10016
Elaine Shum, MD
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Alexander Drilon, MD
- Recruiting
UCI Medical Center
Orange, California, 92868
Misako Nagasaka, MD, PhD
- Recruiting
Stanford Medicine
Palo Alto, California, 94305
Joel Neal, MD, PhD
- Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Jessica Bauman, MD
- Recruiting
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
Jonathan Riess, MD
- Recruiting
University of Washington / Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Christina Baik, MD, MPH
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Saiama Waqar, MD
- Recruiting
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Stephen Liu, MD
Italy7 sites, 6 recruiting
- Recruiting
Università Politecnica Marche
Ancona, 60121
Rossana Berardi, MD
- Completed
IRCCS Istituto Tumori Giovanni Paolo II
Bari, 70124
- Recruiting
Istituto Europeo di Oncologia
Milan, 20141
Gianluca Spitaleri, MD
- Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Matteo Duca, MD
- Recruiting
Istituto Oncologico Veneto
Padova, 35128
Giulia Pasello, MD, PhD
- Recruiting
Ospedale Santa Maria delle Croci
Ravenna, 48121
Chiara Bennati, MD
- Recruiting
Istituto Nazionale Tumori Regina Elena
Rome, 00128
Lorenza Landi, MD
Japan7 sites, 6 recruiting
- Recruiting
Kanagawa Cancer Center
Kanagawa, 241-8515
Shuhei Teranishi, MD, PhD
- Recruiting
Okayama University Hospital
Okayama, 700-8558
Kiichiro Ninomiya, MD, PhD
- Recruiting
Kindai University Hospital
Osaka, 577-8502
Hidetoshi Hayashi, MD, PhD
- Completed
Shizuoka Cancer Center
Shizuoka, 411-8777
- Recruiting
National Cancer Center Hospital
Tokyo, 104-0045
Tatsuya Yoshida, MD, PhD
- Recruiting
The Cancer Institute Hospital Of JFCR
Tokyo, 135-8550
Ryo Ariyasu, MD
- Recruiting
Wakayama Medical University Hospital
Wakayama, 641-8510
Yuhei Harutani, MD
Spain6 sites, 6 recruiting
- Recruiting
University Hospital of A Coruña
A Coruña, 15006
Maria Campelo, MD
- Recruiting
UOMI Cancer Center - Clinica Tres Torres
Barcelona, 08017
Santiago Viteri, MD
- Recruiting
Vall d'Hebron University Hospital
Barcelona, 08035
Enriqueta Felip, MD, PhD
- Recruiting
Gregorio Marañón Hospital
Madrid, 28007
Antonio Calles, MD
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Luis Paz-Ares, MD, PhD
- Recruiting
Hospital Universitario HM Sanchinarro
Madrid, 28050
Ramon Yarza, MD, MBI, MSc
France4 sites, 4 recruiting
- Recruiting
Centre Legon Berard
Lyon, 69008
Aurelie Swalduz, MD
- Recruiting
CHU de Nantes
Nantes, 44000
Elvire Pons-Tostivint, MD, PhD
- Recruiting
Claudius Regaud Institute
Toulouse, 31300
Julien Mazieres, MD, PhD
- Recruiting
Institute Gustave Roussy
Villejuif, 94805
Benjamin Besse, MD, PhD
South Korea4 sites, 4 recruiting
- Recruiting
National Cancer Center
Gyeonggi-do, 10408
Ji-Youn Han, MD
- Recruiting
Seoul National University Hospital
Seoul, 03080
Dong-Wan Kim, MD, PhD
- Recruiting
Yonsei University Health System
Seoul, 03722
Byoung Chul Cho, MD, PhD
- Recruiting
Samsung Medical Center
Seoul, 06351
Sehhoon Park, MD, MS
Taiwan3 sites, 3 recruiting
- Recruiting
Chung Shan Medical University Hospital
Taichung, 40201
Gee Chen Chang, MD, PhD
- Recruiting
National Cheng Kung University Hospital
Tainan, 70403
Chien-Chung Lin, MD, PhD
- Recruiting
National Taiwan University Hospital
Taipei, 10002
Chia-Chi Lin, MD, PhD
Australia2 sites, 2 recruiting
- Recruiting
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Steven Kao, PhD
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Ben Solomon, MD, PhD
Canada2 sites, 2 recruiting
- Recruiting
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Quincy Chu, MD
- Recruiting
Princess Margaret Cancer Research
Toronto, Ontario, M5GG 1L7
Geoffrey Liu, MD
Netherlands2 sites, 2 recruiting
- Recruiting
Netherlands Cancer Institute
Amsterdam, 1066
Joop de Langen, MD, PhD
- Recruiting
University Medical Centre Groningen
Groningen
Anthonie van der Wekken, MD, PhD
Singapore2 sites, 1 recruiting
- Active, not recruiting
National University Hospital Singapore
Singapore, 119074
- Recruiting
National Cancer Centre Singapore
Singapore, 168583
Daniel Tan, PhD
United Kingdom2 sites, 1 recruiting
- Recruiting
Royal Marsden Hospital
London, SW3 6JJ
Sanjay Popat, MBBS, PhD
- Completed
Christie NHS Foundation Trust
Manchester, M20 4BX
Belgium1 site, 1 recruiting
- Recruiting
University Hospital Leuven
Leuven, 3000
Christophe Dooms, MD, PhD
Germany1 site, 1 recruiting
- Recruiting
Cologne University Hospital
Cologne
Juergen Wolf, MD
About this study
Official title: 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)
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.
Read the 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.
- Being tested
- Zidesamtinib (NVL-520)
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zidesamtinib (NVL-520)Drug
Oral tablet of zidesamtinib (NVL-520)
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 dose escalation | Experimental | Zidesamtinib (NVL-520) oral daily dosing Receives: Drug: Zidesamtinib (NVL-520) |
| Cohort 2a | Experimental | ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy Receives: Drug: Zidesamtinib (NVL-520) |
| Cohort 2b | Experimental | ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy Receives: 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 Receives: Drug: Zidesamtinib (NVL-520) |
| Cohort 2d | Experimental | ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy Receives: Drug: Zidesamtinib (NVL-520) |
| Cohort 2e | Experimental | ROS1+ solid tumor and progressed on any prior therapy Receives: Drug: Zidesamtinib (NVL-520) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) (Phase 1)
Highest dose with dose-limiting toxicity (DLT) rate ≤ 25%
Measured: Within 28 days of last patient dosed during dose escalation
Recommended Phase 2 Dose (RP2D)
To determine the RP2D
Measured: Within 28 days of last patient dosed during dose escalation.
Objective Response Rate (ORR) (Phase 2)
To determine ORR as assessed by BICR
Measured: 2-3 years after first patient dosed.
Secondary outcomes (21)
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0
Incidence and severity of treatment-emergent adverse events (TEAEs)
Measured: Approximately 3 years.
Maximum plasma concentration (Cmax) of NVL-520
To determine the maximum plasma concentration (Cmax) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Plasma concentration at the end of the dosing interval (Ctau) of NVL-520
To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Average plasma concentration (Cavg) of NVL-520
To determine the average plasma concentration (Cavg) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Time of maximum concentration (Tmax) of NVL-520
To determine the time of maximum concentration (Tmax) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Area under the curve at the end of the dosing interval (AUCtau) of NVL-520
To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Area under the curve from time 0 to 24 (AUC0-24) of NVL-520
To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Area under the curve from time 0 to infinity (AUCinf) of NVL-520
To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Oral clearance (CL/F) of NVL-520
To determine the oral clearance (CL/F) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Volume of distribution (Vz/F) of NVL-520
To determine the volume of distribution (Vz/F) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Half-life (t1/2) of NVL-520
To determine the half-life (t1/2) of NVL-520
Measured: Pre-dose and up to 24 hours post-dose
Objective response rate (ORR)
Determine ORR as assessed by BICR
Measured: 2-3 years after first patient dosed
Duration of response (DOR)
Determine DOR of NVL-520 until radiographic disease progression or death
Measured: 2-3 years after first patient dosed
Clinical benefit rate (CBR)
Determine CBR of NVL-520
Measured: 2-3 years after first patient dosed
Time to response
Determine time to response of NVL-520
Measured: 2-3 years after first patient dosed
Progression-free survival (PFS)
Determine PFS of NVL-520 until radiographic disease progression or death
Measured: Approximately 3 years
Overall survival (OS)
Determine OS
Measured: Approximately 3 years
Rate of CNS progression
The incidence of CNS as first site of progression, alone or with concurrent extra-CNS progression
Measured: Approximately 3 years
Intracranial objective response rate (IC-ORR)
Determine the intracranial objective response rate
Measured: Approximately 3 years
Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
EORTC QLQ-C30 measures cancer patients' physical, psychological, and social functions. Scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." Higher score for the functioning scales and global health status denotes a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.
Measured: 2-3 years after first patient dosed
Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 module (EORTC QLQ-LC29)
EORTC-QLQ-LC29 measures the quality of life in patients with lung cancer. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." For symptoms scales, higher scores indicated greater symptom burden.
Measured: 2-3 years after first patient dosed
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2021
- Study start4 Jan 2022
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 359 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nuvalent Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vivek Upadhyay, MD, MBI, Study director, Nuvalent Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05118789
- Sponsor's protocol ID
- NVL-520-01
- Status last verified
- Sep 2026
- First submitted
- 19 Oct 2021
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No