NCT05384626Recruiting
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Summary
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
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.
Contacts
The trial team's contact details are shown on request.
See the official trial record- Status
- Recruiting
- Phase
- Phase 1 · Phase 2
- Study type
- Interventional
- Countries
- Switzerland, France, Germany, Italy, United States, Australia, Belgium, Canada, Japan, Netherlands, Singapore, South Korea, Spain, Taiwan, United Kingdom
- Sponsor
- Nuvalent Inc.(Industry)
- Protocol no.
- NVL-655-01
- Conditions
- Locally Advanced Solid Tumor, Metastatic Solid Tumor
- Interventions
- Drug
Treatments studied
- Neladalkib (NVL-655)
- Midazolam
- Repaglinide
- Itraconazole
Locations · 73
- Bellinzona, SwitzerlandIstituto Oncologico Svizzera ItalianaRecruiting at this site
- Lucerne, SwitzerlandLuzerner KantonsspitalRecruiting at this site
- Lyon, FranceCentre Leon BerardRecruiting at this site
- Nantes, FranceChu De NantesRecruiting at this site
- Toulouse, FranceInstitut Claudius RegaudRecruiting at this site
- Villejuif, FranceInstitute Gustave RoussyRecruiting at this site
- Cologne, GermanyUniversitatsklinikum Koln - University Hospital CologneRecruiting at this site
- Frankfurt, GermanyUniversitätsklinikum FrankfurtRecruiting at this site
- Großhansdorf, GermanyLungenClinic Grosshansdorf GmbHRecruiting at this site
- Heidelberg, GermanyUniverskitatsklinikum Heidelberg - University Hospital HeidelbergRecruiting at this site
- Ancona, ItalyAzienda Ospedaliera Universitaria Ospedali Riuniti UmbertoRecruiting at this site
- Bari, ItalyIRCCS Istituto Tumori "G. Paolo II"Recruiting at this site
- Milan, ItalyFondazione IRCCS Istituto Nazionale dei TumoriRecruiting at this site
- Milan, ItalyInstituto Europeo di OncologiaRecruiting at this site
- Padova, ItalyInstituto Oncologico VenetoRecruiting at this site
- Ravenna, ItalyOspedale Santa Maria delle CrociRecruiting at this site
- Rome, ItalyRegina Elena Institute for Cancer ResearchRecruiting at this site
- Orange, United StatesUniversity of California Irvine Medical CenterRecruiting at this site
- Sacramento, United StatesUniversity of California, Davis Comprehensive Cancer CenterRecruiting at this site
- Stanford, United StatesStanford Cancer InstituteRecruiting at this site
- Aurora, United StatesUniversity of Colorado Cancer CenterRecruiting at this site
- Washington D.C., United StatesGeorgetown University Medical CenterRecruiting at this site
- Miami, United StatesUniversity of Miami; Sylvester Cancer CenterRecruiting at this site
- Atlanta, United StatesWinship Cancer Institute, Emory UniversityRecruiting at this site
- Chicago, United StatesUniversity of Chicago Medical CenterRecruiting at this site
- Baltimore, United StatesJohn Hopkins UniversityRecruiting at this site
- Boston, United StatesMassachusetts General HospitalRecruiting at this site
- Boston, United StatesDana Farber Cancer InstituteRecruiting at this site
- Detroit, United StatesHenry Ford Cancer InstituteRecruiting at this site
- St Louis, United StatesWashington University School of Medicine Siteman Cancer CenterRecruiting at this site
In total, worldwide, 73 of the 74 sites listed in the registry are recruiting; the other one is not currently recruiting.
Site status per the ClinicalTrials.gov registry (last update posted: May 27, 2026).
This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.
+ 43 more locations
See also
Other versions
These results are indicative and do not replace medical advice — discuss them with your doctor.