Clinical trial • Phase I/II • Oncology

NVL-655 for Non-small cell lung cancer (advanced) | ALK-positive solid tumors

Phase I/II trial of NVL-655 for Non-small cell lung cancer (advanced) | ALK-positive solid tumors. open-label, none/not specified-controlled, adaptive.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer (advanced) | ALK-positive solid tumors
Trial Stage
Phase I/II
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
01-10-2024
First CTIS Authorization Date
04-11-2024

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial in Belgium, France, Germany and others.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True - Phase 1 includes a dose-escalation dose-finding component to determine RP2D and, if applicable, MTD based on safety/tolerability.
Biomarker Stratified
True, biomarker: ALK rearrangement or activating ALK mutation
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
331

Eligibility

Recruits 331 paediatric patients.

Vulnerable Population
Vulnerable population selected. Minors are included only in Phase 2 Cohort 2f (Age ≥ 12 years and weight > 40 kg). Assent and parental/guardian consent documents are provided (multiple assent forms for ages 12-17 and parental/guardian ICFs are listed among the submitted documents). Dedicated pregnancy-related participant/partner documents are also provided.

Inclusion criteria

  • {"criterion_text":"- Age ≥ 18 years\n- Phase 2 Cohort 2f only: Age ≥ 12 years and weight > 40 kg.\n- Disease criteria: Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation.\n- Disease criteria: Cohorts 2a, 2b, 2c, 2d, and 2e: Histologically or cytologically confirmed locally advanced or metastatic ALK rearrangement or activating ALK mutation\n- Disease criteria: Cohort 2f: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (including NSCLC not eligible for Cohorts 2a-2e) with a documented ALK rearrangement or activating ALK mutation.\n- Prior anticancer treatment: Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1\n- Prior anticancer treatment: Phase 2: Must have measurable disease, defined as ≥1 radiologically measurable target lesion according to RECIST 1.1\n- Pre-treatment tumor tissue\n- Please refer to the protocol for further criteria"}

Exclusion criteria

  • {"criterion_text":"- Patient’s cancer has a known oncogenic driver alteration other than ALK\n- Known allergy/hypersensitivity to excipients of NVL-655\n- Major surgery within 4 weeks of first dose of study drug\n- Ongoing or recent anticancer therapy\n- Ongoing or recent radiation therapy\n- Please refer to the protocol for further criteria"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Phase 1 - Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters","definition_or_measurement_approach":"Incidence and severity of treatment-emergent adverse events (TEAEs) and changes in clinically relevant laboratory parameters as recorded during Phase 1 safety assessments."}
  • {"endpoint_text":"- Phase 1 - RP2D and, if applicable, the MTD","definition_or_measurement_approach":"Determination of the recommended Phase 2 dose (RP2D) and, if applicable, the maximum tolerated dose (MTD) based on Phase 1 dose-escalation safety/tolerability assessments."}
  • {"endpoint_text":"- Phase 2 - ORR according to RECIST 1.1","definition_or_measurement_approach":"Objective response rate (ORR) assessed per RECIST 1.1."}

Secondary endpoints

  • {"endpoint_text":"- Phase 1 - PK parameters of NVL-655","definition_or_measurement_approach":"Pharmacokinetic (PK) parameters of NVL-655 measured in Phase 1 (as listed in secondary objectives/endpoints)."}
  • {"endpoint_text":"- Phase 1 - ORR according to RECIST 1.1 assessment","definition_or_measurement_approach":"Objective response rate (ORR) in Phase 1 assessed per RECIST 1.1."}
  • {"endpoint_text":"- Phase 2 - DOR","definition_or_measurement_approach":"Duration of response (DOR) in Phase 2 (as reported)."}
  • {"endpoint_text":"- Phase 2 - IC-ORR","definition_or_measurement_approach":"Independent Committee-assessed ORR (IC-ORR) in Phase 2."}
  • {"endpoint_text":"- Phase 2 - Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters","definition_or_measurement_approach":"Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters recorded during Phase 2 safety assessments."}
  • {"endpoint_text":"- Phase 2 - PK parameters of NVL-655","definition_or_measurement_approach":"Pharmacokinetic (PK) parameters of NVL-655 measured in Phase 2."}
  • {"endpoint_text":"- Phase 2 - Changes in PROs","definition_or_measurement_approach":"Changes in patient-reported outcomes (PROs) using validated instruments."}

Recruitment

Planned Sample Size
331
Recruitment Window Months
66
Consent Approach
Informed consent obtained from adult participants via dedicated ICFs. For minors (Phase 2 Cohort 2f, aged ≥12 years and ≤17 years), assent forms are provided (assent documents for ages 12-13, 14-17, and Assent 12-17) together with parental/guardian ICFs and parents/guardian data privacy documents. Multiple language versions of ICFs and assent forms are provided (documents include English, French, Dutch, German, Spanish, Italian versions among others). Specific pregnancy-related participant/partner documents are included where applicable.

Methods

  • HCP-facing recruitment materials: 'K2_Recruitment material HCP flyer' (local language versions) — targeted to healthcare professionals/sites to support patient referral.
  • Participant-facing recruitment flyers: 'K2_Recruitment material Participant flyer' (multiple language versions) — targeted to potential participants/patients.
  • Site flyers and patient information leaflets (site- and country-specific) including translated versions for local populations.
  • GP letters, patient cards and diaries noted in subject information materials (used to inform primary care/providers and participants).

Geography

Total Number Of Sites
25
Total Number Of Participants
385

Belgium

Earliest CTIS Part Ii Submission Date
21-10-2024
Latest Decision Or Authorization Date
18-03-2026
Processing Time Days
513
Number Of Sites
2
Number Of Participants
20

Sites

Site Name
Antwerp University Hospital
Department Name
Pulmonary Medicine - Thoracic Oncology
Contact Person Name
Reinier Wener
Contact Person Email
reinier.wener@uza.be
Site Name
UZ Leuven
Department Name
Respiratory Oncology Unit - Respiratory Medicine
Contact Person Name
Christophe Dooms
Contact Person Email
Christophe.dooms@uzleuven.be

France

Earliest CTIS Part Ii Submission Date
21-10-2024
Latest Decision Or Authorization Date
12-03-2026
Processing Time Days
507
Number Of Sites
4
Number Of Participants
110

Sites

Site Name
Oncopole Claudius Regaud
Department Name
Medical Oncology
Contact Person Name
Julien MAZIERES
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Département d’oncologie médicale
Contact Person Name
Elvire Pons-Tostivint
Contact Person Email
elvire.pons@chu-nantes.fr
Site Name
Institut Gustave Roussy
Department Name
Medical Oncology
Contact Person Name
Benjamin BESSE
Site Name
Centre Leon Berard
Department Name
Medical Oncology
Contact Person Name
Aurélie SWALDUZ

Germany

Earliest CTIS Part Ii Submission Date
21-10-2024
Latest Decision Or Authorization Date
06-03-2026
Processing Time Days
501
Number Of Sites
4
Number Of Participants
40

Sites

Site Name
University Hospital Cologne AöR
Department Name
Klinik I für Innere Medizin / LCGC (Lung Cancer Group Cologne)
Contact Person Name
Sebastian Michels
Contact Person Email
sebastian.michels@uk-koeln.de
Site Name
LungenClinic Grosshansdorf GmbH
Department Name
Onkologie
Contact Person Name
Martin Reck
Contact Person Email
m.reck@lungenclinic.de
Site Name
Goethe University Frankfurt
Department Name
Medizinische Klinik II
Contact Person Name
Martin Sebastian
Contact Person Email
sebastian@med.uni-frankfurt.de
Site Name
Thoraxklinik Heidelberg gGmbH
Department Name
Universitätsklinikum Heidelberg
Contact Person Name
Petros Christopoulus

Italy

Earliest CTIS Part Ii Submission Date
21-10-2024
Latest Decision Or Authorization Date
03-04-2026
Processing Time Days
529
Number Of Sites
7
Number Of Participants
95

Sites

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
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 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
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
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
S.C. Medicina Oncologica 1
Contact Person Name
Sara Cresta
Site Name
Istituto Oncologico Veneto
Department Name
Oncologia Medica 2
Contact Person Name
Giulia Pasello
Contact Person Email
giulia.pasello@iov.veneto.it
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Clinica Oncologica
Contact Person Name
Rossana Berardi

Spain

Earliest CTIS Part Ii Submission Date
21-10-2024
Latest Decision Or Authorization Date
07-11-2025
Processing Time Days
382
Number Of Sites
6
Number Of Participants
90

Sites

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 12 De Octubre
Department Name
Oncology
Contact Person Name
Luis Paz-Ares Rodriguez
Contact Person Email
lpazares@hotmail.com
Site Name
Hospital Universitario Hm Sanchinarro
Department Name
Oncology
Contact Person Name
Jose Luis Ramon Patiño
Contact Person Email
jorge.ramon@startmadrid.com
Site Name
Micancer Center S.L.P.
Department Name
Oncology
Contact Person Name
Santiago Viteri Ramirez
Contact Person Email
sviteri@uomi.es
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Oncology
Contact Person Name
Antonio Calles

Sponsor

Primary sponsor

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

Contract research organisations

Name
ICON
Responsibilities
sponsorDuties codes: [4]
Name
WCG Clinical Inc.
Responsibilities
Data monitoring
Name
4g Clinical LLC
Responsibilities
sponsorDuties codes: [3]
Name
Medidata Solutions Inc.
Responsibilities
sponsorDuties codes: [7]

Third parties

  • {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Perficient Inc.","duties_or_roles":"Safety processing","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Greens","duties_or_roles":"Printing services","organisation_type":"Industry"}
  • {"country":"United States","full_name":"ICON","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Health care"}
  • {"country":"United Kingdom","full_name":"Precision For Medicine (UK) Limited","duties_or_roles":"sponsorDuties codes: [1, 12, 2, 6, 9]","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Pharmaspecific","duties_or_roles":"Patient expences reimbursement","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"sponsorDuties codes: [6]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Lab kitting","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Data monitoring","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translation services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Tempus Labs Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Non-Pharmaceutical company"}

Investigational products

Investigational Product Name
NVL-655
Active Substance
NVL-655
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (prodAuthStatus=1)

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