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

Last updated: July 21, 2025
Sponsor: Nuvalent Inc.
Overall Status: Active - Recruiting

Phase

1/2

Condition

Neoplasms

Treatment

NVL-655

Neladalkib (NVL-655)

Clinical Study ID

NCT05384626
NVL-655-01
  • Ages > 12
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. 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 metastaticsolid tumor with a documented ALK rearrangement or activating ALK mutation.

  3. Phase 2

  4. Phase 2 Cohorts except 2f: Histologically or cytologically confirmed locallyadvanced or metastatic NSCLC with a documented ALK rearrangement

  5. Phase 2 Cohort 2f: Histologically or cytologically confirmed locally advancedor metastatic solid tumor with a documented ALK rearrangement or activating ALKmutation detected by certified assay.

  6. Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1Phase 2: Must have measurable disease according to RECIST 1.1

  7. Adequate organ function and bone marrow reserve

Exclusion

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 anothertherapeutic clinical study.

Study Design

Total Participants: 840
Treatment Group(s): 2
Primary Treatment: NVL-655
Phase: 1/2
Study Start date:
June 09, 2022
Estimated Completion Date:
January 31, 2028

Study Description

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.

Connect with a study center

  • Royal North Shore Hospital

    Saint Leonards, New South Wales 2065
    Australia

    Site Not Available

  • Royal North Shore Hospital

    Sydney, New South Wales 2065
    Australia

    Active - Recruiting

  • Princess Alexandra Hospital

    Woolloongabba, Queensland 4102
    Australia

    Active - Recruiting

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria 3000
    Australia

    Active - Recruiting

  • Universitair Ziekenhuis Antwerpen (UZA)

    Antwerp, 2650
    Belgium

    Active - Recruiting

  • Universitaire Ziekenhuizen Leuven Campus Gastthuisberg

    Leuven, 3000
    Belgium

    Active - Recruiting

  • Cross Cancer Institute

    Edmonton, Alberta T6G 1Z2
    Canada

    Active - Recruiting

  • BC Cancer Center

    Vancouver, British Columbia VZ 4E6
    Canada

    Active - Recruiting

  • The Ottawa Hospital Cancer Center

    Ottawa, Ontario K1H 8L6
    Canada

    Active - Recruiting

  • Princess Margaret Cancer Centre

    Toronto, Ontario M5G 0A3
    Canada

    Active - Recruiting

  • BC Cancer

    Vancouver, VZ 4E6
    Canada

    Active - Recruiting

  • Centre Leon Berard

    Lyon, 69373
    France

    Active - Recruiting

  • Chu De Nantes

    Nantes, 44093
    France

    Active - Recruiting

  • Chu De Nantes

    Saint-Herblain, 44800
    France

    Site Not Available

  • Institut Claudius Regaud

    Toulouse Cedex, 31059
    France

    Active - Recruiting

  • Institute Gustave Roussy

    Villejuif, 94805
    France

    Active - Recruiting

  • Universitatsklinikum Koln - University Hospital Cologne

    Cologne, 50937
    Germany

    Active - Recruiting

  • Universitätsklinikum Frankfurt

    Frankfurt, 60590
    Germany

    Active - Recruiting

  • LungenClinic Grosshansdorf GmbH

    Grosshansdorf, 22927
    Germany

    Active - Recruiting

  • Universkitatsklinikum Heidelberg - University Hospital Heidelberg

    Heidelberg, 69126
    Germany

    Active - Recruiting

  • Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto

    Ancona, 60126
    Italy

    Active - Recruiting

  • IRCCS Istituto Tumori "G. Paolo II"

    Bari, 70124
    Italy

    Active - Recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133
    Italy

    Active - Recruiting

  • Instituto Europeo di Oncologia

    Milano, 20141
    Italy

    Active - Recruiting

  • Instituto Oncologico Veneto

    Padova, 35128
    Italy

    Active - Recruiting

  • Ospedale Santa Maria delle Croci

    Ravenna, 48100
    Italy

    Active - Recruiting

  • Regina Elena Institute for Cancer Research

    Rome, 00144
    Italy

    Active - Recruiting

  • Instituto Oncologico Veneto

    Veneto,
    Italy

    Site Not Available

  • Kanagawa Cancer Center

    Kanagawa, 2418515
    Japan

    Active - Recruiting

  • Okayama University Hospital

    Okayama, 7008558
    Japan

    Active - Recruiting

  • Kindai University Hospital

    Osaka, 5898511
    Japan

    Active - Recruiting

  • Shizuoka Cancer Center

    Shizuoka, 4118777
    Japan

    Active - Recruiting

  • Center Institute Hospital of JFCR

    Tokyo, 1358550
    Japan

    Active - Recruiting

  • National Cancer Center Hospital

    Tokyo, 1040051
    Japan

    Active - Recruiting

  • Wakayama Medical University Hospital

    Wakayama, 6418510
    Japan

    Active - Recruiting

  • National Cancer Center

    Goyang-si, Gyeonggi-do 10408
    Korea, Republic of

    Active - Recruiting

  • Samsung Medical Center

    Seoul, 06351
    Korea, Republic of

    Active - Recruiting

  • Seoul National University Hospital

    Seoul, 03080
    Korea, Republic of

    Active - Recruiting

  • Severance Hospital Yonsei University Health System

    Seoul, 03722
    Korea, Republic of

    Active - Recruiting

  • The Netherlands Cancer Institute

    Amsterdam, 1066 CX
    Netherlands

    Active - Recruiting

  • University Medical Center Groningen (UMCG)

    Groningen, 9713 GZ
    Netherlands

    Active - Recruiting

  • National Cancer Centre Singapore

    Singapore, 168583
    Singapore

    Active - Recruiting

  • National University Hospital

    Singapore, 119074
    Singapore

    Active - Recruiting

  • Complejo Hospitalario Universitario de A Coruna

    A Coruña, 15006
    Spain

    Active - Recruiting

  • UOMI Cancer Center

    Barcelona, 08017
    Spain

    Active - Recruiting

  • Vall d'Hebron

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28009
    Spain

    Active - Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041
    Spain

    Active - Recruiting

  • Istituto Oncologico Svizzera Italiana

    Bellinzona, 6500
    Switzerland

    Active - Recruiting

  • Luzerner Kantonsspital

    Luzern, 6000
    Switzerland

    Active - Recruiting

  • Luzerner Kantonsspital

    Spitalstrasse,
    Switzerland

    Site Not Available

  • Chung-Shan Medical University Hospital

    Taichung City, 402306
    Taiwan

    Active - Recruiting

  • National Cheng Kung University Hospital

    Tainan, 70403
    Taiwan

    Active - Recruiting

  • National Taiwan University Hospital

    Taipei, 10002
    Taiwan

    Active - Recruiting

  • Royal Marsden Hospital

    Sutton, Surrey SM2 5PT
    United Kingdom

    Active - Recruiting

  • Edinburgh Cancer Centre

    Edinburgh, EH4 2XU
    United Kingdom

    Active - Recruiting

  • The Royal Marsden - Chelsea

    London, SM2 5PT
    United Kingdom

    Active - Recruiting

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX
    United Kingdom

    Active - Recruiting

  • University of California Irvine Medical Center

    Orange, California 92868
    United States

    Active - Recruiting

  • University of California, Davis Comprehensive Cancer Center

    Sacramento, California 95817
    United States

    Active - Recruiting

  • Stanford Cancer Institute

    Stanford, California 94305
    United States

    Active - Recruiting

  • University of Colorado Cancer Center

    Aurora, Colorado 80045
    United States

    Active - Recruiting

  • University of Colorado Cancer Center

    Denver, Colorado 80045
    United States

    Site Not Available

  • Georgetown University Medical Center

    Washington, District of Columbia 20007
    United States

    Active - Recruiting

  • University of Miami; Sylvester Cancer Center

    Miami, Florida 33136
    United States

    Active - Recruiting

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

  • University of Chicago Medical Center

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • John Hopkins University

    Baltimore, Maryland 21224
    United States

    Active - Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • Mass General Hospital

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • Henry Ford Cancer Institute

    Detroit, Michigan 48202
    United States

    Active - Recruiting

  • Washington University School of Medicine Siteman Cancer Center

    Saint Louis, Missouri 63310
    United States

    Active - Recruiting

  • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

    New York, New York 10016
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York 10065
    United States

    Active - Recruiting

  • Duke University Medical Center

    Durham, North Carolina 27705
    United States

    Active - Recruiting

  • OSU Brain & Spine Hospital

    Columbus, Ohio 43210
    United States

    Active - Recruiting

  • University of Pennsylvania, Abramson Cancer Center

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • Sarah Cannon

    Nashville, Tennessee 37203
    United States

    Active - Recruiting

  • MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Site Not Available

  • Fred Hutchinson Cancer Center

    Seattle, Washington 98109
    United States

    Active - Recruiting

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