RecruitingPhase 1Phase 2NCT05384626

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

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)


Sponsor

Nuvalent Inc.

Enrollment

840 participants

Start Date

Jun 9, 2022

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 12 Years

Inclusion Criteria7

  • Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing \>40 kg.
  • Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation.
  • Phase 2
  • Phase 2 Cohorts except 2f: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
  • 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.
  • 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
  • Adequate organ function and bone marrow reserve

Exclusion Criteria5

  • Patient's cancer has a known oncogenic driver alteration other than ALK.
  • Known allergy/hypersensitivity to excipients of NVL-655.
  • Major surgery within 4 weeks of the study entry
  • Ongoing or anticancer therapy
  • Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.

Interventions

DRUGNeladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)


Locations(74)

University of California Irvine Medical Center

Orange, California, United States

University of California, Davis Comprehensive Cancer Center

Sacramento, California, United States

Stanford Cancer Institute

Stanford, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

University of Miami; Sylvester Cancer Center

Miami, Florida, United States

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, United States

John Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Cancer Institute

Detroit, Michigan, United States

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

OSU Brain & Spine Hospital

Columbus, Ohio, United States

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Sarah Cannon

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Royal North Shore Hospital

Sydney, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Universitair Ziekenhuis Antwerpen (UZA)

Antwerp, Belgium

Universitaire Ziekenhuizen Leuven Campus Gastthuisberg

Leuven, Belgium

Cross Cancer Institute

Edmonton, Alberta, Canada

BC Cancer Center

Vancouver, British Columbia, Canada

The Ottawa Hospital Cancer Center

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Centre Leon Berard

Lyon, France

Chu De Nantes

Nantes, France

Institut Claudius Regaud

Toulouse, France

Institute Gustave Roussy

Villejuif, France

Universitatsklinikum Koln - University Hospital Cologne

Cologne, Germany

Universitätsklinikum Frankfurt

Frankfurt, Germany

LungenClinic Grosshansdorf GmbH

Großhansdorf, Germany

Universkitatsklinikum Heidelberg - University Hospital Heidelberg

Heidelberg, Germany

Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto

Ancona, Italy

IRCCS Istituto Tumori "G. Paolo II"

Bari, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Instituto Europeo di Oncologia

Milan, Italy

Instituto Oncologico Veneto

Padua, Italy

Ospedale Santa Maria delle Croci

Ravenna, Italy

Regina Elena Institute for Cancer Research

Rome, Italy

Kanagawa Cancer Center

Kanagawa, Japan

Okayama University Hospital

Okayama, Japan

Kindai University Hospital

Osaka, Japan

Shizuoka Cancer Center

Shizuoka, Japan

National Cancer Center Hospital

Tokyo, Japan

Cancer Institute Hospital of JFCR

Tokyo, Japan

Wakayama Medical University Hospital

Wakayama, Japan

The Netherlands Cancer Institute

Amsterdam, Netherlands

University Medical Center Groningen (UMCG)

Groningen, Netherlands

National University Hospital

Singapore, Singapore, Singapore

National Cancer Centre Singapore

Singapore, Singapore, Singapore

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Seoul National University Hospital

Seoul, South Korea

Severance Hospital Yonsei University Health System

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

Complejo Hospitalario Universitario de A Coruna

A Coruña, Spain

UOMI Cancer Center

Barcelona, Spain

Vall d'Hebron

Barcelona, Spain

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, Spain

Istituto Oncologico Svizzera Italiana

Bellinzona, Switzerland

Luzerner Kantonsspital

Lucerne, Switzerland

Chung-Shan Medical University Hospital

Taichung, Taiwan

National Cheng Kung University Hospital

Tainan, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Edinburgh Cancer Centre

Edinburgh, United Kingdom

The Royal Marsden - Chelsea

London, United Kingdom

The Christie NHS Foundation Trust

Manchester, United Kingdom

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