Clinical trial • Phase I/II • Oncology|Rare Disease

ZIDESAMTINIB for Advanced ROS1-positive non-small cell lung cancer (NSCLC) | Advanced ROS1-positive solid tumors

Phase I/II trial of ZIDESAMTINIB for Advanced ROS1-positive non-small cell lung cancer (NSCLC) | Advanced ROS1-positive solid tumors. adaptive.

Overview

Trial Therapeutic Area
Oncology|Rare Disease
Trial Disease
Advanced ROS1-positive non-small cell lung cancer (NSCLC) | Advanced ROS1-positive solid tumors
Trial Stage
Phase I/II
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
18-03-2024
First CTIS Authorization Date
23-04-2024

Trial design

adaptive Phase I/II trial in Belgium, France, Germany and others.

Adaptive
True, dose-escalation/adaptive elements present: Phase 1 dose-escalation to determine RP2D and, if applicable, MTD based on incidence of DLTs during Cycle 1, overall safety profile, PK, PD, and preliminary efficacy (interim safety/PK evaluations inform dose decisions).
Biomarker Stratified
True, biomarker: ROS1 rearrangement; strata/cohorts: phase 1 dose-escalation and Phase 2 expansion cohorts including Cohorts 2a/2b/2c/2d (NSCLC-specific cohorts) and Cohort 2e (other ROS1-positive solid tumors).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
317

Eligibility

Recruits 317 paediatric patients.

Vulnerable Population
Vulnerable population considerations are included: minors/adolescents are addressed (Phase 2 Cohort 2e allows age ≥12 years). The dossier includes minor-specific assent and parent/guardian consent documents (e.g. 'L1_SIS and ICF_Minors Study Assent_Redacted', 'L1_SIS and ICF_Parents Guardian Main_Redacted', 'L1_SIS and ICF_Parents Guardian Data Privacy_Redacted'), indicating assent and parental/guardian consent handling for underage participants.

Inclusion criteria

  • {"criterion_text":"- 1. Age ≥18 years a. Phase 2 Cohort 2e only: Age ≥12 years."}
  • {"criterion_text":"- 2. Disease criteria a. Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement. b. Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic ROS1 rearrangement. c. Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (including NSCLC not eligible for Cohorts 2a-2d) with ROS1 rearrangement."}
  • {"criterion_text":"- 3. Prior anticancer treatment"}
  • {"criterion_text":"- 4. Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1. Phase 2: Must have measurable disease, defined as ≥1 radiologically measurable target lesion according to RECIST 1.1."}
  • {"criterion_text":"- 5. Pre-treatment tumor tissue. Please refer to the protocol for further criteria."}

Exclusion criteria

  • {"criterion_text":"- Patients meeting any of the following criteria will be excluded from the study:"}
  • {"criterion_text":"- 1. Patient’s cancer has a known oncogenic driver alteration other than ROS1."}
  • {"criterion_text":"- 2. Known allergy/hypersensitivity to excipients of NVL-520."}
  • {"criterion_text":"- 3. Major surgery within 4 weeks of first dose of study drug."}
  • {"criterion_text":"- 4. Ongoing or recent anticancer therapy."}
  • {"criterion_text":"- Please refer to the protocol for further criteria."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Phase 1 • RP2D and, if applicable, the MTD as determined by incidence of DLTs during Cycle 1, overall safety profile, PK, PD, and preliminary efficacy Phase 2 • ORR per RECIST 1.1.","definition_or_measurement_approach":"Phase 1: Determination of RP2D and, if applicable, MTD based on incidence of dose-limiting toxicities (DLTs) during Cycle 1, overall safety, PK, PD and preliminary efficacy. Phase 2: Objective response rate (ORR) measured per RECIST 1.1."}

Secondary endpoints

  • {"endpoint_text":"- • Incidence and severity of treatment-emergent adverse events (TEAEs) and changes in clinically relevant laboratory parameters","definition_or_measurement_approach":"TEAEs incidence and severity graded per standard toxicity criteria; changes in clinically relevant laboratory parameters as captured on scheduled labs (see protocol)."}
  • {"endpoint_text":"- • Pharmacokinetic parameters of NVL-520 − Maximum plasma concentration (Cmax); Cmax – dose normalized, plasma concentration at the end of the dosing interval (Ctau); average plasma concentration (Cavg); time of maximum concentration (Tmax); Please refer to protocol for further end points due to word limitation.","definition_or_measurement_approach":"PK parameters measured from plasma sampling according to the PK sampling schedule (Cmax, dose-normalized Cmax, Ctau, Cavg, Tmax); detailed methods in protocol."}

Recruitment

Planned Sample Size
317
Recruitment Window Months
61
Consent Approach
Adults provide informed consent via the provided ICFs. For minors (Phase 2 Cohort 2e, age ≥12 years), assent is obtained using a minors' assent form and parental/guardian consent is required (documents include 'L1_SIS and ICF_Minors Study Assent_Redacted', 'L1_SIS and ICF_Parents Guardian Main_Redacted', 'L1_SIS and ICF_Parents Guardian Data Privacy_Redacted'). Consent/ICF documents are available in multiple languages as evidenced by file listings (examples include Dutch, French, English, Spanish, Italian, German).

Geography

Total Number Of Sites
21
Total Number Of Participants
283

Belgium

Earliest CTIS Part Ii Submission Date
28-03-2024
Latest Decision Or Authorization Date
19-01-2026
Processing Time Days
662
Number Of Sites
1
Number Of Participants
20

Sites

Site Name
UZ Leuven
Department Name
Department of Respiratory Oncology
Contact Person Name
Christophe Dooms
Contact Person Email
christophe.dooms@uzleuven.be

France

Earliest CTIS Part Ii Submission Date
28-03-2024
Latest Decision Or Authorization Date
19-01-2026
Processing Time Days
662
Number Of Sites
4
Number Of Participants
100

Sites

Site Name
Institut Gustave Roussy
Department Name
Oncologie médicale
Contact Person Name
Benjamin Besse
Site Name
Institut Claudius Regaud / Oncopole / CHU Toulouse
Department Name
Oncologie
Contact Person Name
Julien Mazières
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Oncologie médicale
Contact Person Name
Elvire Pons-Tostivint
Contact Person Email
elvire.pons@chu-nantes.fr
Site Name
Centre Leon Berard
Department Name
Oncologie médicale
Contact Person Name
Aurélie Swalduz

Germany

Earliest CTIS Part Ii Submission Date
28-03-2024
Latest Decision Or Authorization Date
21-01-2026
Processing Time Days
664
Number Of Sites
1
Number Of Participants
25

Sites

Site Name
University Hospital Cologne AöR
Department Name
Oncology
Contact Person Name
Jürgen Wolf
Contact Person Email
juergen.wolf@uk-koeln.de

Italy

Earliest CTIS Part Ii Submission Date
28-03-2024
Latest Decision Or Authorization Date
19-01-2026
Processing Time Days
662
Number Of Sites
7
Number Of Participants
40

Sites

Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
S.C. Medicina Oncologica 1
Contact Person Name
Matteo Duca
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
U.O. Oncologia
Contact Person Name
Chiara Bennati
Contact Person Email
chiara.bennati@auslromagna.it
Site Name
Istituto Tumori Bari Giovanni Paolo II
Department Name
SSD Oncologia Medica per la Patologia Toracica
Contact Person Name
Domenico Galetta
Contact Person Email
galetta@oncologico.bari.it
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
UOSD Sperimentazioni cliniche Fase 1 e Medicina di precisione
Contact Person Name
Lorenza Landi
Contact Person Email
lorenza.landi@ifo.it
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Divisione di Oncologia Toracica
Contact Person Name
Gianluca Spitaleri
Contact Person Email
gianluca.spitaleri@ieo.it
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Clinica Oncologica
Contact Person Name
Rossana Berardi
Site Name
Istituto Oncologico Veneto
Department Name
Oncologia Medica 2
Contact Person Name
Giulia Pasello
Contact Person Email
giulia.pasello@iov.veneto.it

Netherlands

Earliest CTIS Part Ii Submission Date
28-03-2024
Latest Decision Or Authorization Date
26-01-2026
Processing Time Days
669
Number Of Sites
2
Number Of Participants
42

Sites

Site Name
Universitair Medisch Centrum Groningen
Department Name
Dept. of Pulmonology and Tuberculosis
Contact Person Name
A.J. van der Wekken
Contact Person Email
a.j.van.der.wekken@umcg.nl
Site Name
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Department Name
Pulmonology
Contact Person Name
Adrianus Johannes de Langen
Contact Person Email
thoraxmanagement@nki.nl

Spain

Earliest CTIS Part Ii Submission Date
28-03-2024
Latest Decision Or Authorization Date
23-01-2026
Processing Time Days
666
Number Of Sites
6
Number Of Participants
56

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Contact Person Name
Luis Paz-Ares Rodriguez
Contact Person Email
lpazares@hotmail.com
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Oncology
Contact Person Name
Antonio Calles
Site Name
Micancer Center S.L.P.
Department Name
Oncology
Contact Person Name
Santiago Viteri Ramirez
Contact Person Email
sviteri@uomi.es
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Oncology
Contact Person Name
Maria Rosario Garcia Campelo
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Contact Person Name
Enriqueta Felip Font
Contact Person Email
efelip@vhio.net
Site Name
Hospital Universitario Hm Sanchinarro
Department Name
Oncology
Contact Person Name
Ramon Yarza
Contact Person Email
Ramon.yarza@startmadrid.com

Sponsor

Primary sponsor

Full Name
Nuvalent Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research LLC
Responsibilities
Central imaging storage and analysis
Name
WCG Clinical Inc.
Responsibilities
Responsible for providing system for collection of patient reported outcome
Name
4g Clinical LLC
Responsibilities
code 3

Third parties

  • {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"PK Analyses","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"PD Analyses","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Tempus Labs Inc.","duties_or_roles":"Tumor NGS testing","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"code 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"PD Analyses","organisation_type":"Pharmaceutical company"}
  • {"country":"Hungary","full_name":"Precision for Medicine (HU) Kft.","duties_or_roles":"codes 1,12,2,5,6,9","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Responsible for providing system for collection of patient reported outcome","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Icon Clinical Research LLC","duties_or_roles":"Central imaging storage and analysis","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
NVL-520
Active Substance
ZIDESAMTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL

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