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En studie av NVL-655 hos pasienter med avansert NSCLC og andre solide svulster som har ALK-omorganisering eller aktiverer ALK-mutasjon (ALKOVE-1)

4. november 2026 oppdatert av: Nuvalent Inc.

En fase 1/2-studie av den selektive anaplastiske lymfomkinase (ALK)-hemmeren NVL-655 hos pasienter med avansert NSCLC og andre solide svulster (ALKOVE-1)

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

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

840

Fase

  • Fase 2
  • Fase 1

Utvidet tilgang

Tilgjengelig utenfor den kliniske utprøvingen. Se utvidet tilgangspost.

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2065
        • Rekruttering
        • Royal North Shore Hospital
        • Hovedetterforsker:
          • Malinda Itchins, MBBS PhD
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Rekruttering
        • Princess Alexandra Hospital
        • Hovedetterforsker:
          • Kenneth O'Byrne, MD
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Rekruttering
        • Peter MacCallum Cancer Centre
        • Hovedetterforsker:
          • Benjamin Solomon, MD, PhD
  • Belgia
      • Antwerp, Belgia, 2650
        • Rekruttering
        • Universitair Ziekenhuis Antwerpen (UZA)
        • Hovedetterforsker:
          • Reinier Wener, MD
      • Leuven, Belgia, 3000
        • Rekruttering
        • Universitaire Ziekenhuizen Leuven Campus Gastthuisberg
        • Hovedetterforsker:
          • Christophe Dooms, MD
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Rekruttering
        • Cross Cancer Institute
        • Hovedetterforsker:
          • Quincy Siu Chung Chu, MD
    • British Columbia
      • Vancouver, British Columbia, Canada, VZ 4E6
        • Rekruttering
        • BC Cancer Center
        • Hovedetterforsker:
          • Jamie Feng, MD
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Rekruttering
        • The Ottawa Hospital Cancer Center
        • Hovedetterforsker:
          • Garth Nicholas, MD
      • Toronto, Ontario, Canada, M5G 0A3
        • Rekruttering
        • Princess Margaret Cancer Centre
        • Hovedetterforsker:
          • Geoffrey Liu, M.D.
  • Forente stater
    • California
      • Orange, California, Forente stater, 92868
        • Rekruttering
        • University of California Irvine Medical Center
        • Hovedetterforsker:
          • Misako Nagasaka, MD
      • Sacramento, California, Forente stater, 95817
        • Rekruttering
        • University of California, Davis Comprehensive Cancer Center
        • Hovedetterforsker:
          • Jonathan Riess, MD
      • Stanford, California, Forente stater, 94305
        • Rekruttering
        • Stanford Cancer Institute
        • Hovedetterforsker:
          • Joel Neal, MD, PhD
    • Colorado
      • Aurora, Colorado, Forente stater, 80045
        • Rekruttering
        • University of Colorado Cancer Center
        • Hovedetterforsker:
          • Ross Camidge, MD, PhD
    • District of Columbia
      • Washington D.C., District of Columbia, Forente stater, 20007
        • Rekruttering
        • Georgetown University Medical Center
        • Hovedetterforsker:
          • Joshua Reuss, MD
    • Florida
      • Miami, Florida, Forente stater, 33136
        • Rekruttering
        • University of Miami; Sylvester Cancer Center
        • Hovedetterforsker:
          • Gilberto de Lima Lopes, MD
    • Georgia
      • Atlanta, Georgia, Forente stater, 30322
        • Rekruttering
        • Winship Cancer Institute, Emory University
        • Hovedetterforsker:
          • Ticiana Leal, MD
    • Illinois
      • Chicago, Illinois, Forente stater, 60637
        • Rekruttering
        • University of Chicago Medical Center
        • Hovedetterforsker:
          • Marina Garassino, MD
    • Maryland
      • Baltimore, Maryland, Forente stater, 21224
        • Rekruttering
        • John Hopkins University
        • Hovedetterforsker:
          • Vincent Lam, MD
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02114
        • Rekruttering
        • Massachusetts General Hospital
        • Hovedetterforsker:
          • Jessica Lin, MD
      • Boston, Massachusetts, Forente stater, 02215
        • Rekruttering
        • Dana Farber Cancer Institute
        • Hovedetterforsker:
          • Alice Shaw, MD
    • Michigan
      • Detroit, Michigan, Forente stater, 48202
        • Rekruttering
        • Henry Ford Cancer Institute
        • Hovedetterforsker:
          • Bindu Potugari, MD
    • Missouri
      • St Louis, Missouri, Forente stater, 63310
        • Rekruttering
        • Washington University School of Medicine Siteman Cancer Center
        • Hovedetterforsker:
          • Saiama Waqar, MD
    • New York
      • New York, New York, Forente stater, 10065
        • Rekruttering
        • Memorial Sloan Kettering Cancer Center
        • Hovedetterforsker:
          • Alexander Drilon, MD
      • New York, New York, Forente stater, 10016
        • Rekruttering
        • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
        • Hovedetterforsker:
          • Elaine Shum, MD
    • North Carolina
      • Durham, North Carolina, Forente stater, 27705
        • Rekruttering
        • Duke University Medical Center
        • Hovedetterforsker:
          • Thomas Stinchcombe, MD
    • Ohio
      • Columbus, Ohio, Forente stater, 43210
        • Rekruttering
        • OSU Brain & Spine Hospital
        • Hovedetterforsker:
          • Logan Roof, MD, MSCR
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater, 19104
        • Rekruttering
        • University of Pennsylvania, Abramson Cancer Center
        • Hovedetterforsker:
          • Charu Aggarwal, MD
    • Tennessee
      • Nashville, Tennessee, Forente stater, 37203
        • Rekruttering
        • Sarah Cannon
        • Hovedetterforsker:
          • Melissa Johnson, MD
    • Texas
      • Houston, Texas, Forente stater, 77030
        • Aktiv, ikke rekrutterende
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, Forente stater, 98109
        • Rekruttering
        • Fred Hutchinson Cancer Center
        • Hovedetterforsker:
          • Christina Baik, MD, MPH
  • Frankrike
      • Lyon, Frankrike, 69373
        • Rekruttering
        • Centre Leon Berard
        • Hovedetterforsker:
          • Aurelie Swalduz, MD
      • Nantes, Frankrike, 44093
        • Rekruttering
        • Chu De Nantes
        • Hovedetterforsker:
          • Elvire Pons-Tostivint, MD, PhD
      • Toulouse, Frankrike, 31059
        • Rekruttering
        • Institut Claudius Regaud
        • Hovedetterforsker:
          • Julien Mazieres, MD, PhD
      • Villejuif, Frankrike, 94805
        • Rekruttering
        • Institute Gustave Roussy
        • Hovedetterforsker:
          • Benjamin Besse, MD, PhD
  • Italia
      • Ancona, Italia, 60126
        • Rekruttering
        • Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto
        • Hovedetterforsker:
          • Rossana Berardi, MD
      • Bari, Italia, 70124
        • Rekruttering
        • IRCCS Istituto Tumori "G. Paolo II"
        • Hovedetterforsker:
          • Domenico Galetta, MD
      • Milan, Italia, 20133
        • Rekruttering
        • Fondazione IRCCS Istituto Nazionale dei Tumori
        • Hovedetterforsker:
          • Sara Cresta, MD
      • Milan, Italia, 20141
        • Rekruttering
        • Instituto Europeo di Oncologia
        • Hovedetterforsker:
          • Gianluca Spitaleri, MD
      • Padova, Italia, 35128
        • Rekruttering
        • Instituto Oncologico Veneto
        • Hovedetterforsker:
          • Giulia Pasello, MD
      • Ravenna, Italia, 48100
        • Rekruttering
        • Ospedale Santa Maria delle Croci
        • Hovedetterforsker:
          • Chiara Bennati, MD
      • Rome, Italia, 00144
        • Rekruttering
        • Regina Elena Institute for Cancer Research
        • Hovedetterforsker:
          • Lorenza Landi, MD
  • Japan
      • Kanagawa, Japan, 2418515
        • Rekruttering
        • Kanagawa Cancer Center
        • Hovedetterforsker:
          • Tetsuro Kondo, MD
      • Okayama, Japan, 7008558
        • Rekruttering
        • Okayama University Hospital
        • Hovedetterforsker:
          • Kiichiro Ninomiya, MD
      • Osaka, Japan, 5898511
        • Rekruttering
        • Kindai University Hospital
        • Hovedetterforsker:
          • Junko Tanizaki, MD
      • Shizuoka, Japan, 4118777
        • Rekruttering
        • Shizuoka Cancer Center
        • Hovedetterforsker:
          • Ryo Ko, MD PhD
      • Tokyo, Japan, 1040051
        • Rekruttering
        • National Cancer Center Hospital
        • Hovedetterforsker:
          • Tatsuya Yoshida, MD
      • Tokyo, Japan, 1358550
        • Rekruttering
        • Cancer Institute Hospital of JFCR
        • Hovedetterforsker:
          • Ryo Ariyasu, MD
      • Wakayama, Japan, 6418510
        • Rekruttering
        • Wakayama Medical University Hospital
        • Hovedetterforsker:
          • Hiroaki Akamatsu, MD, PhD
  • Nederland
      • Amsterdam, Nederland, 1066 CX
        • Rekruttering
        • The Netherlands Cancer Institute
        • Hovedetterforsker:
          • Adrianus Joop de Langen, MD
      • Groningen, Nederland, 9713 GZ
        • Rekruttering
        • University Medical Center Groningen (UMCG)
        • Hovedetterforsker:
          • AJ Van Der Wekken, MD
  • Singapore
    • Singapore
      • Singapore, Singapore, Singapore, 119074
        • Rekruttering
        • National University Hospital
        • Hovedetterforsker:
          • Ross Soo, MD
      • Singapore, Singapore, Singapore, 168583
        • Rekruttering
        • National Cancer Centre Singapore
        • Hovedetterforsker:
          • Aaron Tan, MD
  • Spania
      • A Coruña, Spania, 15006
        • Rekruttering
        • Complejo Hospitalario Universitario de A Coruna
        • Hovedetterforsker:
          • Maria Campelo, MD
      • Barcelona, Spania, 08035
        • Rekruttering
        • Vall d'Hebron
        • Hovedetterforsker:
          • Enriqueta Felip, Md, PhD
      • Barcelona, Spania, 08017
        • Rekruttering
        • UOMI Cancer Center
        • Hovedetterforsker:
          • Santiago Viteri Ramirez, MD PhD
      • Madrid, Spania, 28041
        • Rekruttering
        • Hospital Universitario 12 de Octubre
        • Hovedetterforsker:
          • Luis Paz Ares, MD, PhD
      • Madrid, Spania, 28009
        • Rekruttering
        • Hospital General Universitario Gregorio Maranon
        • Hovedetterforsker:
          • Antonio Calles, MD
  • Storbritannia
      • Edinburgh, Storbritannia, EH4 2XU
        • Rekruttering
        • Edinburgh Cancer Centre
        • Hovedetterforsker:
          • Colin Barrie, MD
      • London, Storbritannia, SM2 5PT
        • Rekruttering
        • The Royal Marsden - Chelsea
        • Hovedetterforsker:
          • Sanjay Popat MD
      • Manchester, Storbritannia, M20 4BX
        • Rekruttering
        • The Christie NHS Foundation Trust
        • Hovedetterforsker:
          • Matthew Krebs, MB ChB PhD
    • Surrey
      • Sutton, Surrey, Storbritannia, SM2 5PT
        • Rekruttering
        • Royal Marsden Hospital
        • Hovedetterforsker:
          • Sanjay Popat MD
  • Sveits
      • Bellinzona, Sveits, 6500
        • Rekruttering
        • Istituto Oncologico Svizzera Italiana
        • Hovedetterforsker:
          • Patrizia Froesch, MD
      • Lucerne, Sveits, 6000
        • Rekruttering
        • Luzerner Kantonsspital
        • Hovedetterforsker:
          • Anna Allemann, MD
  • Sør -Korea
      • Seoul, Sør -Korea, 03080
        • Rekruttering
        • Seoul National University Hospital
        • Hovedetterforsker:
          • Dong-wan Kim, MD
      • Seoul, Sør -Korea, 06351
        • Rekruttering
        • Samsung Medical Center
        • Hovedetterforsker:
          • Myung-Ju Ahn, MD
      • Seoul, Sør -Korea, 03722
        • Rekruttering
        • Severance Hospital Yonsei University Health System
        • Hovedetterforsker:
          • Byoung Chul Cho, MD
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, Sør -Korea, 10408
        • Rekruttering
        • National Cancer Center
        • Hovedetterforsker:
          • Ji-Youn Han, MD
  • Taiwan
      • Taichung, Taiwan, 402306
        • Rekruttering
        • Chung-Shan Medical University Hospital
        • Hovedetterforsker:
          • Gee-Chen Chang, MD
      • Tainan, Taiwan, 70403
        • Rekruttering
        • National Cheng Kung University Hospital
        • Hovedetterforsker:
          • Chien-Chung Lin, MD
      • Taipei, Taiwan, 10002
        • Rekruttering
        • National Taiwan University Hospital
        • Hovedetterforsker:
          • Josh Lin, MD
  • Tyskland
      • Cologne, Tyskland, 50937
        • Rekruttering
        • Universitatsklinikum Koln - University Hospital Cologne
        • Hovedetterforsker:
          • Dr med Sebastian Michels
      • Frankfurt, Tyskland, 60590
        • Rekruttering
        • Universitätsklinikum Frankfurt
        • Hovedetterforsker:
          • Martin Sebastian, MD
      • Großhansdorf, Tyskland, 22927
        • Rekruttering
        • LungenClinic Grosshansdorf GmbH
        • Hovedetterforsker:
          • Prof Dr Martin Reck
      • Heidelberg, Tyskland, 69126
        • Rekruttering
        • Universkitatsklinikum Heidelberg - University Hospital Heidelberg
        • Hovedetterforsker:
          • Prof Dr med Petros Christopoulos

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

12 år og eldre (Barn, Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Phase 1 dose escalation

Neladalkib (NVL-655) oral daily dosing
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)
Eksperimentell: 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.
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)
Eksperimentell: 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.
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)
Eksperimentell: 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.
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)
Eksperimentell: 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.
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)
Eksperimentell: Cohort 2e

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)
Eksperimentell: 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.
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)
Eksperimentell: Cohort G (DDI sub-study)

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)

Legemiddel: Midazolam

Oral Solution of Midazolam

Legemiddel: Repaglinide

Oral Tablet of Repaglinide
Eksperimentell: Cohort H (DDI sub-study)

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI
Legemiddel: Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)

Legemiddel: Itraconazole

Oral Solution of Itraconazole

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Objective Response Rate (ORR) (Phase 2)
Tidsramme: 2-3 years after first patient dosed.

To determine ORR as assessed by BICR
2-3 years after first patient dosed.
Dose limiting toxicities (DLTs) (Phase 1)
Tidsramme: Within the first 21 days of the first neladalkib (NVL-655) dose

Define the dose limiting toxicities (DLTs)
Within the first 21 days of the first neladalkib (NVL-655) dose
Recommended Phase 2 Dose (RP2D) (Phase 1)
Tidsramme: Within 21 days of last patient dosed during escalation

To determine the RP2D
Within 21 days of last patient dosed during escalation
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)
Tidsramme: Approximately 3 years

Incidence and severity of treatment-emergent adverse events (TEAEs)
Approximately 3 years
Area under the curve of repaglinide (Phase 2 DDI sub-study)
Tidsramme: 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
Pre-dose and up to 24 hours post-dose
Area under the curve of midazolam (Phase 2 DDI sub-study)
Tidsramme: 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
Pre-dose and up to 24 hours post-dose
Area under the curve of neladalkib (NVL-655) (Phase 2 DDI sub-study)
Tidsramme: 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)
Pre-dose and up to 24 hours post-dose

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Maximum plasma concentration, (Cmax) of neladalkib (NVL-655)
Tidsramme: Pre-dose and up to 24 hours post-dose

To determine the maximum plasma concentration (Cmax) of neladalkib (NVL-655)
Pre-dose and up to 24 hours post-dose
Plasma concentration at the end of the dosing interval (Ctau) of neladalkib (NVL-655)
Tidsramme: 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)
Pre-dose and up to 24 hours post-dose
Average plasma concentration (Cavg) of neladalkib (NVL-655)
Tidsramme: Pre-dose and up to 24 hours post-dose

To determine the average plasma concentration (Cavg) of neladalkib (NVL-655)
Pre-dose and up to 24 hours post-dose
Time of maximum concentration (Tmax) of neladalkib (NVL-655)
Tidsramme: Pre-dose and up to 24 hours post-dose

To determine the time of maximum concentration (Tmax) of neladalkib (NVL-655)
Pre-dose and up to 24 hours post-dose
Area under the curve at the end of the dosing interval (AUCtau) of neladalkib (NVL-655)
Tidsramme: 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)
Pre-dose and up to 24 hours post-dose
Area under the curve from time 0 to 24 (AUC0-24) of neladalkib (NVL-655)
Tidsramme: 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)
Pre-dose and up to 24 hours post-dose
Area under the curve from time 0 to infinity (AUCinf) of neladalkib (NVL-655)
Tidsramme: 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)
Pre-dose and up to 24 hours post-dose
Oral clearance (CL/F) of neladalkib (NVL-655)
Tidsramme: Pre-dose and up to 24 hours post-dose

To determine the oral clearance (CL/F) of neladalkib (NVL-655)
Pre-dose and up to 24 hours post-dose
Volume of distribution (Vz/F) of neladalkib (NVL-655)
Tidsramme: Pre-dose and up to 24 hours post-dose

To determine the volume of distribution (Vz/F) of neladalkib (NVL-655)
Pre-dose and up to 24 hours post-dose
Half-life (t1/2) of neladalkib (NVL-655)
Tidsramme: Pre-dose and up to 24 hours post-dose

To determine the half-life (t1/2) of neladalkib (NVL-655)
Pre-dose and up to 24 hours post-dose
Objective response rate (ORR) (Phase 1)
Tidsramme: 2-3 years after first patient dosed

Determine ORR as assessed by Investigator
2-3 years after first patient dosed
Duration of response (DOR)
Tidsramme: 2-3 years after first patient dosed

Determine DOR of neladalkib (NVL-655) until radiographic disease progression or death
2-3 years after first patient dosed
Clinical benefit rate (CBR)
Tidsramme: 2-3 years after first patient dosed

Determine CBR of neladalkib (NVL-655)
2-3 years after first patient dosed
Time to response
Tidsramme: Approximately 3 years

Determine time to response of neladalkib (NVL-655)
Approximately 3 years
Progression-free survival (PFS)
Tidsramme: 2-3 years after first patient dosed

Determine PFS of neladalkib (NVL-655) until radiographic disease progression or death
2-3 years after first patient dosed
Overall survival (OS) (Phase 2)
Tidsramme: Approximately 3 years

Determine OS
Approximately 3 years
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2)
Tidsramme: Approximately 3 years

Incidence and severity of treatment-emergent adverse events (TEAEs)
Approximately 3 years
Quality of life assessment
Tidsramme: 2-3 years after first patient dosed

Measure the quality of life in patients with cancer and/or lung cancer.
2-3 years after first patient dosed
Incidence and severity of AEs and incidence of abnormalities across laboratory values, ECGs, vital signs, and physical examinations (Phase 2 DDI-sub-study)
Tidsramme: Up to 3 months after last dose

Assess the safety and tolerability of neladalkib (NVL-655) when co-administered with repaglinide or midazolam
Up to 3 months after last dose
Incidence and severity of AEs and incidence of abnormalities across laboratory values, ECGs, vital signs, and physical examinations (Phase 2 DDI-sub-study)
Tidsramme: Up to 3 months after last dose

Assess the safety and tolerability of neladalkib (NVL-655) when co-administered with itraconazole
Up to 3 months after last dose

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Nuvalent Inc.

Etterforskere

  • Studieleder: Viola Zhu, MD, PHD, Nuvalent Inc.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

9. juni 2022

Primær fullføring (Antatt)

1. desember 2027

Studiet fullført (Antatt)

1. januar 2028

Datoer for studieregistrering

Først innsendt

17. mai 2022

Først innsendt som oppfylte QC-kriteriene

17. mai 2022

Først lagt ut (Faktiske)

20. mai 2022

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

6. november 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

4. november 2026

Sist bekreftet

1. november 2026

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • NVL-655-01

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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