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

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

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.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 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. Step 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. Step 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. Step 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 trial?

9 criteria

  • 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 trial?

13 criteria

  • 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
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Investigated drugs

  • 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.

What is already known about the treatment

  • NVL-655

    An investigational selective Anaplastic Lymphoma Kinase (ALK) inhibitor being studied in clinical trials for the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). This oral medication works by specifically targeting and blocking the ALK protein that drives cancer growth in patients with ALK gene alterations. Currently undergoing Phase 3 clinical trials as a first-line treatment option, comparing its efficacy against alectinib in treatment-naïve patients with advanced NSCLC.

  • Alectinib

    An established oral medication belonging to the class of ALK inhibitors, approved for treating ALK-positive non-small cell lung cancer (NSCLC). The drug works by blocking the activity of the abnormal ALK protein, thereby helping to slow or stop the growth of cancer cells. It is currently used as a standard first-line treatment option for patients with advanced ALK-positive NSCLC and has demonstrated significant efficacy in clinical practice.

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 detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-517553-26-00Protocol codeNVL-655-04Estimated enrolment450 patientsSponsorNuvalent Inc.

sourced from the EU Clinical Trials Register and site verification

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