A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)

NCT05384626
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
840
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Lead sponsor
Nuvalent Inc.
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Start date
2022-06-09
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Number of sites
74
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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
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Short 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)
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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)
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2028-01-01
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First posted
2022-05-20
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Registry last updated
2026-05-27
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Primary completion date
2027-12-01
clinicaltrials.gov
Start date
2022-06-09
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Participants
840
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Participant count basis
Estimated
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Planned participants
840
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Protocol amendments
6
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Number of sites
74
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Nuvalent Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05384626
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ClinicalTrials.gov ID
NCT05384626
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Dose limiting toxicities (DLTs) (Phase 1)

    Timeframe: Within the first 21 days of the first neladalkib (NVL-655) dose

    Define the dose limiting toxicities (DLTs)

  2. Recommended Phase 2 Dose (RP2D) (Phase 1)

    Timeframe: Within 21 days of last patient dosed during escalation

    To determine the RP2D

  3. Objective Response Rate (ORR) (Phase 2)

    Timeframe: 2-3 years after first patient dosed.

    To determine ORR as assessed by BICR

  4. Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)

    Timeframe: Approximately 3 years

    Incidence and severity of treatment-emergent adverse events (TEAEs)

  5. Area under the curve of repaglinide (Phase 2 DDI sub-study)

    Timeframe: 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

  6. Area under the curve of midazolam (Phase 2 DDI sub-study)

    Timeframe: 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

  7. Area under the curve of neladalkib (NVL-655) (Phase 2 DDI sub-study)

    Timeframe: 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)

  1. Maximum plasma concentration, (Cmax) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the maximum plasma concentration (Cmax) of neladalkib (NVL-655)

  2. Plasma concentration at the end of the dosing interval (Ctau) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the plasma concentration at the end of the dosing interval (Ctau) of neladalkib (NVL-655)

  3. Average plasma concentration (Cavg) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the average plasma concentration (Cavg) of neladalkib (NVL-655)

  4. Time of maximum concentration (Tmax) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the time of maximum concentration (Tmax) of neladalkib (NVL-655)

  5. Area under the curve at the end of the dosing interval (AUCtau) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the area under the curve at the end of the dosing interval (AUCtau) of neladalkib (NVL-655)

  6. Area under the curve from time 0 to 24 (AUC0-24) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the area under the curve from time 0 to 24 (AUC0-24) of neladalkib (NVL-655)

  7. Area under the curve from time 0 to infinity (AUCinf) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the area under the curve from time 0 to infinity (AUCinf) of neladalkib (NVL-655)

  8. Oral clearance (CL/F) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the oral clearance (CL/F) of neladalkib (NVL-655)

  9. Volume of distribution (Vz/F) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the volume of distribution (Vz/F) of neladalkib (NVL-655)

  10. Half-life (t1/2) of neladalkib (NVL-655)

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the half-life (t1/2) of neladalkib (NVL-655)

  11. Objective response rate (ORR) (Phase 1)

    Timeframe: 2-3 years after first patient dosed

    Determine ORR as assessed by Investigator

  12. Duration of response (DOR)

    Timeframe: 2-3 years after first patient dosed

    Determine DOR of neladalkib (NVL-655) until radiographic disease progression or death

  13. Clinical benefit rate (CBR)

    Timeframe: 2-3 years after first patient dosed

    Determine CBR of neladalkib (NVL-655)

  14. Time to response

    Timeframe: Approximately 3 years

    Determine time to response of neladalkib (NVL-655)

  15. Progression-free survival (PFS)

    Timeframe: 2-3 years after first patient dosed

    Determine PFS of neladalkib (NVL-655) until radiographic disease progression or death

  16. Overall survival (OS) (Phase 2)

    Timeframe: Approximately 3 years

    Determine OS

  17. Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2)

    Timeframe: Approximately 3 years

    Incidence and severity of treatment-emergent adverse events (TEAEs)

  18. Quality of life assessment

    Timeframe: 2-3 years after first patient dosed

    Measure the quality of life in patients with cancer and/or lung cancer.

  19. Incidence and severity of AEs and incidence of abnormalities across laboratory values, ECGs, vital signs, and physical examinations (Phase 2 DDI-sub-study)

    Timeframe: Up to 3 months after last dose

    Assess the safety and tolerability of neladalkib (NVL-655) when co-administered with repaglinide or midazolam

  20. Incidence and severity of AEs and incidence of abnormalities across laboratory values, ECGs, vital signs, and physical examinations (Phase 2 DDI-sub-study)

    Timeframe: Up to 3 months after last dose

    Assess the safety and tolerability of neladalkib (NVL-655) when co-administered with itraconazole

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Children, Adults, Older adults
Minimum age
12 Years
Healthy volunteers
No

  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

  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.
Sources for eligibility
clinicaltrials.gov

  • University of California Irvine Medical CenterOrange, United StatesRecruiting
  • University of California, Davis Comprehensive Cancer CenterSacramento, United StatesRecruiting
  • Stanford Cancer InstituteStanford, United StatesRecruiting
  • University of Colorado Cancer CenterAurora, United StatesRecruiting
  • Georgetown University Medical CenterWashington D.C., United StatesRecruiting
  • University of Miami; Sylvester Cancer CenterMiami, United StatesRecruiting
  • Winship Cancer Institute, Emory UniversityAtlanta, United StatesRecruiting
  • University of Chicago Medical CenterChicago, United StatesRecruiting
  • John Hopkins UniversityBaltimore, United StatesRecruiting
  • Massachusetts General HospitalBoston, United StatesRecruiting
  • Dana Farber Cancer InstituteBoston, United StatesRecruiting
  • Henry Ford Cancer InstituteDetroit, United StatesRecruiting
  • Washington University School of Medicine Siteman Cancer CenterSt Louis, United StatesRecruiting
  • Laura & Isaac Perlmutter Cancer Center at NYU Langone HealthNew York, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • Duke University Medical CenterDurham, United StatesRecruiting
  • OSU Brain & Spine HospitalColumbus, United StatesRecruiting
  • University of Pennsylvania, Abramson Cancer CenterPhiladelphia, United StatesRecruiting
  • Sarah CannonNashville, United StatesRecruiting
  • MD Anderson Cancer CenterHouston, United StatesActive, not recruiting
  • Fred Hutchinson Cancer CenterSeattle, United StatesRecruiting
  • Royal North Shore HospitalSydney, AustraliaRecruiting
  • Princess Alexandra HospitalWoolloongabba, AustraliaRecruiting
  • Peter MacCallum Cancer CentreMelbourne, AustraliaRecruiting
  • Universitair Ziekenhuis Antwerpen (UZA)Antwerp, BelgiumRecruiting

And 49 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Related records

Drugs (4)

Lead sponsors (1)

Targets (18)