Study comparing NVL-655 to alectinib in untreated patients with ALK-positive advanced non-small cell lung cancer

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What is this study about?

This study focuses on patients with advanced non-small cell lung cancer (NSCLC) that is ALK-positive. ALK-positive means the cancer has a specific genetic change in the anaplastic lymphoma kinase gene. The study compares two medications: an experimental drug called NVL-655 and an approved medication called Alecensa (alectinib). These medications belong to a group of drugs called ALK inhibitors, which target the specific genetic change found in this type of lung cancer.

The purpose of this research is to evaluate how well NVL-655 works compared to Alecensa in patients who have not received any previous treatment for their advanced lung cancer. Both medications are taken by mouth in the form of tablets or capsules. The study will measure how long patients live without their cancer getting worse and track any side effects that may occur during treatment.

During the study, participants will be randomly assigned to receive either NVL-655 or Alecensa. The treatment may continue for up to several years, depending on how well it works for each patient. Throughout the study, patients will have regular medical check-ups and imaging scans to monitor their cancer. The study will also look at how the treatments affect patients’ quality of life and whether the medications work on cancer that has spread to the brain.

1 Initial assessment

Your eligibility for the study will be confirmed through medical tests showing non-small cell lung cancer (NSCLC) that is locally advanced or has spread to other parts of the body

A test will confirm the presence of ALK gene rearrangement in your tissue or blood sample

Your doctor will verify that you have not received any prior systemic treatment for NSCLC

A tissue sample from your tumor will be required (either existing or new)

Your physical condition will be evaluated using the ECOG scale (a measure of daily living abilities)

2 Treatment assignment

You will be randomly assigned to receive either NVL-655 tablets or Alecensa capsules (alectinib)

Both medications are taken by mouth

The exact dosing schedule will be provided by your healthcare team

3 Regular monitoring

Your cancer progression will be regularly assessed through imaging scans

Your response to treatment will be evaluated using standardized criteria

Blood tests will be performed to monitor your health

You will complete questionnaires about your health and symptoms

Any side effects will be monitored and recorded

4 Treatment duration

Treatment will continue until your disease progresses

Treatment may also be stopped if unacceptable side effects occur

The study is planned to run until October 2029

Who Can Join the Study?

  • Must have confirmed advanced or metastatic non-small cell lung cancer (cancer that has spread and cannot be treated with combined therapies)
  • Must have a positive test for ALK gene rearrangement (a specific genetic change in the cancer cells) from either tissue or blood sample
  • Must not have received any previous systemic treatment for lung cancer, except:
    • May have had chemotherapy before or after surgery if it was completed at least 12 months before study entry
    • Must never have received ALK inhibitor drugs (like alectinib) at any time
  • Must have at least one tumor that can be measured using standard imaging techniques
  • Must be able to provide a tumor tissue sample (either previously collected or from a new biopsy)
  • Must have good physical function ability, rated as ECOG 0-2 (able to care for self and be up and about more than half of waking hours)
  • Must be an adult (18 years or older)
  • Can be either male or female

Who Cannot Join the Study?

  • Age under 18 years
  • History of treatment with any ALK inhibitor (medications that target ALK-positive lung cancer)
  • Active brain metastases (cancer that has spread to the brain) that are not stable or require steroids
  • History of other cancers within the past 3 years, except for successfully treated non-melanoma skin cancer or cervical cancer in situ
  • Significant heart problems, including:
    • Uncontrolled high blood pressure
    • Heart attack within past 6 months
    • Unstable heart rhythm disorders
  • Severe liver problems or abnormal liver function tests
  • Known HIV infection, active hepatitis B, or active hepatitis C
  • Any serious medical condition that could interfere with study participation
  • Pregnant or breastfeeding women
  • Unable to swallow oral medications
  • Participation in another clinical trial within 28 days before starting this study

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name City Country Status
Medizinische Universitaet Innsbruck Innsbruck Austria
Institut Gustave Roussy Villejuif France
IRCCS Humanitas Research Hospital Rozzano Italy
Lungenfachklinik Immenhausen Germany
Centre Hospitalier Universitaire De Bordeaux Bordeaux France
Oncopole Claudius Regaud Toulouse France
Katholieke Universiteit te Leuven Leuven Belgium

Other Sites

Site Name City Country Status
Istituto Oncologico Veneto Padua Italy
Istituto Europeo Di Oncologia S.r.l. Milan Italy
Hospital General Universitario Gregorio Maranon Madrid Spain
Hospital Universitario 12 De Octubre Madrid Spain
HELIOS Klinikum Emil von Behring GmbH Berlin Germany
Istituto Tumori Bari Giovanni Paolo II Bari Italy
Instituto Portugues De Oncologia Do Porto Francisco Gentil E.P.E. Porto Portugal
Bekes Varmegyei Koezponti Korhaz Gyula Hungary
Szpital Specjalistyczny W Brzozowie Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza Brzozow Poland
Klinikum Esslingen GmbH Esslingen Am Neckar Germany
Fondazione IRCCS San Gerardo Dei Tintori Monza Italy
LungenClinic Grosshansdorf GmbH Grosshansdorf Germany
MVZ-Onkologie Velbert GbR Velbert Germany
Henry Dunant Hospital Center Athens Greece
Micancer Center S.L.P. Barcelona Spain
One Day Med Sp. z o.o. Szczecin Poland
General University Hospital Of Larissa Larissa Greece
University Of Debrecen Debrecen Hungary
Matrai Gyogyintezet Gyongyos Hungary
Ospedale S G Moscati Statte Italy
Virgen del Rocío University Hospital Sevilla Spain
Odense University Hospital Odense Denmark
Universitair Medisch Centrum Utrecht Utrecht The Netherlands
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS Candiolo Italy
Stichting Radboud University Medical Center Nijmegen The Netherlands
Champalimaud Clinical Centre Lisbon Portugal
Universita’ Di Pisa Pisa Italy
Universita’ Politecnica Delle Marche Ancona Italy
Nemocnice AGEL Novy Jicin a.s. Novy Jicin Czechia
Centre Hospitalier Universitaire De Nantes Nantes France
Region Midtjylland Aarhus Denmark
Azienda Unita Sanitaria Locale Della Romagna Faenza Italy
Netherlands Cancer Institute Amsterdam The Netherlands
Hopital Beaujon Clichy France
Stadt Wien Wiener Gesundheitsverbund Vienna Austria
Fondazione I.R.C.C.S. Istituto Neurologico Besta Milan Italy
Centre Francois Baclesse Caen France
Hospital CUF Porto S.A. Porto Portugal
Genesis Mikti Idiotiki Kliniki Gynaikas A.E. Maieutiki Gynaikologiki Cheirourgiki Thessaloniki Greece
Csfifbwzx Ujlbfrxjhekfeb Skzdmznuo Woluwe-Saint-Lambert Belgium
Irteytuh Rvhzhazo Da Ccawma Di Mtxgopgisnm Montpellier France
Zmjhjvm Mqofqsp Ceyygw Sxs z oacq Lublin Poland
Ckssaw Lwiw Bzqbbf Lyon France
Ibhbjm Isnqczlq Fbslmqvskwszk Oznyezsgvly Rome Italy
Iiqfyzds Cepjaf Dubyuaoqmswdrnyek L'hospitalet De Llobregat Spain
Mzzacards siormx Horovice Czechia
Bmwdqcmtokn Vixttwbdg Ohudfdbkfimw Kecskemet Hungary
Loqey Ghfaxyb Hhgonwqt Oz Azuumg Athens Greece
Hkmgte Hkyzinak Herlev Denmark
Ievkgkrk Rguedfhep Pox Lp Smxgxs Don Thteol Dxya Agszowt Iagf Snnxhe Meldola Italy
Acstpdecpr Pxtzbrwr Hbxjmmqv Do Mlquzryka Marseille France
Adjnnn Mfwiowu Cofbsu Sotm Thessaloniki Greece
Kxjmfybm dpn Urqawhefbzas Mdziwhpo Apy Munich Germany
Gvit Szwtu Pjlxpaomr Cxotoli Sigk Cascais Portugal
Upizsibszzhhva Cbslbbm Krkusrbuq Gdansk Poland
Ukynohksxr Om Amlrxdv Edegem Belgium
Cbygrm Hwvcciaayhw Rlbivrpx Djdmioatiwmzmt Angers France
Hfrccood Usujgigfrwkne dr A Chbfyn A Coruna Galicia Spain

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
Austria Austria
Recruiting
15.11.2025
Belgium Belgium
Recruiting
15.11.2025
Czechia Czechia
Recruiting
15.11.2025
Denmark Denmark
Recruiting
15.11.2025
France France
Recruiting
15.11.2025
Germany Germany
Recruiting
15.11.2025
Greece Greece
Recruiting
15.11.2025
Hungary Hungary
Recruiting
15.11.2025
Italy Italy
Recruiting
15.11.2025
Poland Poland
Recruiting
15.11.2025
Portugal Portugal
Recruiting
15.11.2025
Spain Spain
Recruiting
15.11.2025
The Netherlands The Netherlands
Recruiting
15.11.2025

Trial locations

NVL-655 is a new selective Anaplastic Lymphoma Kinase (ALK) inhibitor. It is being studied as a treatment for advanced non-small cell lung cancer in patients who have not received previous treatment. This medication works by targeting specific proteins that are involved in cancer cell growth.

Alectinib is an established ALK inhibitor medication used to treat non-small cell lung cancer. It works by blocking specific signals that cancer cells use to grow and spread. It is currently used as a standard treatment for patients with ALK-positive lung cancer.

Investigated diseases:

Non-small cell lung cancer (NSCLC) – A type of lung cancer that begins in the cells of the lungs and forms in the tissues of the lung, typically in the cells lining air passages. It develops when healthy cells in the lung change and grow out of control, forming a mass called a tumor. NSCLC specifically refers to several types of lung cancers that behave in similar ways, with the ALK-positive variant being characterized by a specific genetic change in the anaplastic lymphoma kinase (ALK) gene. The disease can spread from its original location to other parts of the body through the blood or lymph system. As the cancer progresses, it may affect breathing and other bodily functions.

Trial ID:
2024-517553-26-00
Protocol code:
NVL-655-04
NCT ID:
NCT06765109
Trial Phase:
Therapeutic confirmatory (Phase III)

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