UPCC 19523 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)

Study of an Investigational ALK Inhibitor in Advanced NSCLC and Other Tumors

Enrolling By Invitation
12 years or above
All
Phase 1/2
840 participants needed
1 Location

Brief description of study

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.

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

Detailed description of study

In Phase 2, study patients will be enrolled into 6 distinct cohorts:

  • Cohort 2a: 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.
  • Cohort 2b: 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.
  • Cohort 2c: 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.
  • Cohort 2d: 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.
  • Cohort 2e: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
  • Cohort 2f: 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.

In the DDI sub-study, study patients will be enrolled into 2 distinct cohorts:

  • Cohort G (DDI sub-study with midazolam and repaglinide): Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI.
  • Cohort H (DDI sub-study with itraconazole): Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Locally Advanced Solid Tumor, Metastatic Solid Tumor
  • Age: 12 years or above
  • Gender: All

Inclusion Criteria:

  1. 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
  2. Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation.
  3. Phase 2
    1. Phase 2 Cohorts except 2f: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
    2. 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.
  4. DDI sub-study cohorts: Histologically or cytologically confirmed locally advanced or

    metastatic NSCLC with a documented ALK rearrangement

  5. 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
  6. 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
  7. Adequate organ function and bone marrow reserve

Exclusion criteria:

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

This study investigates an investigational medication for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors that have a specific change in the anaplastic lymphoma kinase (ALK) gene. The purpose of this study is to find out how safe and tolerable the investigational medication is, and to determine the best dose for further research. The study is divided into two phases: Phase 1 will focus on assessing safety and identifying the suitable dose, while Phase 2 will evaluate how well the medication works in shrinking tumors.

Participants will be divided into different study arms based on their previous treatments and specific ALK gene changes. They will receive the investigational medication and be monitored for any side effects and the medication's effectiveness. The study will include regular health checks and assessments to track the progress and response of the tumors to the treatment.

  • Who can participate: Adults aged 18 and older, and adolescents aged 12 and older in certain cases, with advanced solid tumors or NSCLC with ALK gene changes may participate. Participants must have measurable or evaluable disease and adequate organ function. Individuals with other cancer gene changes or allergies to the investigational medication's components are excluded.
  • Study details: Participants will take part in different study arms based on their previous treatments and specific ALK gene changes. An inactive substance that looks like the investigational medicine but does not contain any medicine is not used in this study.
Updated on 27 May 2026. Study ID: 23-1717
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