NCT05384626 · Nuvalent Inc.
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
What this study is about
Phase 1/2, gradually increasing doses and expansion study designed to evaluate the safety and how well patients handle the treatment 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.
View original scientific description
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.
Interventions
DRUG
Neladalkib (NVL-655)
Oral Tablet of Neladalkib (NVL-655)
DRUG
Midazolam
Oral Solution of Midazolam
DRUG
Repaglinide
Oral Tablet of Repaglinide
DRUG
Itraconazole
Oral Solution of Itraconazole
Primary outcome measures
Dose limiting toxicities (DLTs) (Phase 1)
Time frame: Within the first 21 days of the first neladalkib (NVL-655) dose
Define the dose limiting toxicities (DLTs)
Recommended Phase 2 Dose (RP2D) (Phase 1)
Time frame: Within 21 days of last patient dosed during escalation
To determine the RP2D
Objective Response Rate (ORR) (Phase 2)
Time frame: 2-3 years after first patient dosed.
To determine ORR as assessed by BICR
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)
Time frame: Approximately 3 years
Incidence and severity of treatment-emergent adverse events (TEAEs)
Area under the curve of repaglinide (Phase 2 DDI sub-study)
Time frame: Pre-dose and up to 24 hours post-dose
To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of repaglinide
Area under the curve of midazolam (Phase 2 DDI sub-study)
Time frame: Pre-dose and up to 24 hours post-dose
To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of midazolam
Area under the curve of neladalkib (NVL-655) (Phase 2 DDI sub-study)
Time frame: Pre-dose and up to 24 hours post-dose
To determine the effect of itraconazole on the single oral dose PK of neladalkib (NVL-655)
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing \>40 kg. 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. 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 5. Adequate organ function and bone marrow reserve
Exclusion criteria
- Patient's cancer has a known oncogenic driver alteration other than ALK. 2. Known allergy/hypersensitivity to excipients of NVL-655. 3. Major surgery with
Where
- Orange, California
- Sacramento, California
- Stanford, California
- Aurora, Colorado
- Washington D.C., District of Columbia
- Miami, Florida
- Atlanta, Georgia
- Chicago, Illinois
- Baltimore, Maryland
- Boston, Massachusetts
- Detroit, Michigan
- St Louis, Missouri
And 7 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 27, 2026 · Source of record for eligibility and locations