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Taking people in ItalyPhase 1/2

Tests neladalkib in patients aged 12 and older with advanced ALK-positive cancers

Tests neladalkib in people with advanced ALK-positive lung cancer or other solid tumors.

Key facts

Who runs it
Nuvalent Inc.
Where
Ancona, Bari, Milan, Padova, Ravenna, and Rome, ItalySee the 7 sitesAlso in 14 other countries, 68 sites
Registry title
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Status
Recruiting
Phase
Phase 1/2
People taking part
840 people, planned
Started
9 Jun 2022
Expected to end
Jan 2028
Type of study
Interventional, 9 groups
Treatments tested
  • Neladalkib (NVL-655)
  • Midazolam
  • Repaglinide
  • Itraconazole
Record updated
6 November 2026

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults, and some teenagers, with advanced lung cancer or another solid tumor that has an ALK gene change. It tests the drug neladalkib (NVL-655).

Age
18 years or older. One group (Phase 2 Cohort 2f) takes people 12 years or older who weigh more than 40 kg (88 lb). Two drug-interaction groups (Cohorts G and H) take ages 18 to 60.
Sex
All sexes can join.
Disease stage
Locally advanced or metastatic cancer. Phase 1 takes any solid tumor with an ALK change. Phase 2 mostly takes non-small cell lung cancer (NSCLC) with an ALK rearrangement. Cohort 2f takes any solid tumor with an ALK change. The disease must be measurable (Phase 2) or evaluable (Phase 1).
Earlier treatment
The drug-interaction groups need at least 1 earlier ALK TKI and no earlier trial drug aimed at ALK. Any amount of earlier chemotherapy or immunotherapy is fine for them.
Biomarker or test result
A documented ALK rearrangement or activating ALK mutation, found by a certified test.

Main reasons for not taking part

  • Cancer with a known driver gene change other than ALK
  • Known allergy to the ingredients of NVL-655
  • Major surgery within 4 weeks before entering the trial
  • Ongoing anticancer therapy
  • Receiving treatment in another clinical trial

The registry criteria, word for word

Show all 12 criteriaShow less

Who can take part

  • Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing >40 kg. DDI sub-study Cohorts G and H only: age 18-60 years, inclusive
  • Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation
  • Phase 2; Phase 2 Cohorts except 2f: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement; Phase 2 Cohort 2f: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation detected by certified assay
  • DDI sub-study cohorts: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
  • DDI sub-study cohorts: Must have previously received ≥1 ALK TKI; no prior investigational agents targeting ALK; any number of prior chemotherapy and/or immunotherapy
  • 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 organ function and bone marrow reserve

Who cannot take part

  • Major surgery within 4 weeks of the study entry
  • Ongoing or anticancer therapy
  • Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study
  • Patient's cancer has a known oncogenic driver alteration other than ALK
  • Known allergy/hypersensitivity to excipients of NVL-655

Where in Italy

Also in 14 other countries, 68 sites

  • Azienda Ospedaliero-Universitaria delle MarcheAncona, ItalyTaking people
  • Istituto Tumori Bari Giovanni Paolo IIBari, ItalyTaking people
  • Fondazione IRCCS - Istituto Nazionale dei TumoriMilan, ItalyTaking people
  • Istituto Europeo di Oncologia s.r.lMilan, ItalyTaking people
  • Istituto Oncologico VenetoPadova, ItalyTaking people
  • Azienda Unità Sanitaria Locale della RomagnaRavenna, ItalyTaking people
  • I.F.O. Istituti Fisioterapici OspitalieriRome, ItalyTaking people

About the trial

What the trial wants to find out

Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of neladalkib (NVL-655), determine the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced ALK- positive (ALK+) NSCLC and other solid tumors.

Read full original descriptionShow less

Phase 1 will evaluate the overall safety and tolerability of neladalkib and will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of neladalkib in patients with advanced ALK+ solid tumors.

Phase 2 will determine the objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) of neladalkib 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 neladalkib in patients with advanced ALK-positive NSCLC and other solid tumors.

A drug-drug interaction (DDI) sub-study will determine the effect of neladalkib on the pharmacokinetics of midazolam and repaglinide, as well as the effect of itraconazole on the pharmacokinetics of neladalkib, in patients with advanced ALK-positive NSCLC

The 9 groups in the trial

  • Phase 1 dose escalationTreatment being tested

    Neladalkib (NVL-655) oral daily dosing

    Treatment: Neladalkib (NVL-655)

  • Cohort 2aTreatment being tested

    Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received 1 prior 2nd-generation ALK TKI (ceritinib, alectinib, or brigatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.

    Treatment: Neladalkib (NVL-655)

  • Cohort 2bTreatment being tested

    Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.

    Treatment: Neladalkib (NVL-655)

  • Cohort 2cTreatment being tested

    Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received lorlatinib as the only prior ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy received prior to lorlatinib is allowed.

    Treatment: Neladalkib (NVL-655)

  • Cohort 2dTreatment being tested

    Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who are naïve to ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy is allowed.

    Treatment: Neladalkib (NVL-655)

  • Cohort 2eTreatment being tested

    Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.

    Treatment: Neladalkib (NVL-655)

  • Cohort 2fTreatment being tested

    Patients with other solid tumors harboring an ALK rearrangement or activating ALK mutation, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists.

    Treatment: Neladalkib (NVL-655)

  • Cohort G (DDI sub-study)Treatment being tested

    Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI

    Treatment: Neladalkib (NVL-655), Midazolam, and Repaglinide

  • Cohort H (DDI sub-study)Treatment being tested

    Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI

    Treatment: Neladalkib (NVL-655) and Itraconazole

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov and on the EU's official list of trials (CTIS).
Official title
A Phase 1/2 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors (ALKOVE-1)
Plain-language title
Tests neladalkib in patients aged 12 and older with advanced ALK-positive cancersGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Record updated
6 November 2026