Back to Trials
NCT06765109PHASE3Recruiting

Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLC

Nuvalent Inc.

Start Date

7/17/2025

Completion Date

12/1/2029

Summary

Multicenter, randomized, controlled, open-label, Phase 3 study designed to demonstrate that neladalkib (NVL-655) is superior to alectinib in prolonging progression-free survival (PFS) in patients with treatment-naïve, Anaplastic Lymphoma Kinase (ALK) positive, advanced Non-Small Cell Lung Cancer (NSCLC).

Detailed Description

Patients will be randomized in a 1:1 ratio (approximately 225 in each arm) to receive either neladalkib (NVL-655) or alectinib.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Histologically or cytologically confirmed locally advanced (not amenable for multimodality treatment) or metastatic Non-small Cell Lung Cancer (NSCLC) 2. Documented Anaplastic Lymphoma Kinase (ALK) rearrangement via testing of tissue or blood 3. No prior systemic anticancer treatment for NSCLC (adjuvant/neoadjuvant chemotherapy allowed if 12 months prior to randomization; prior ALK tyrosine kinase inhibitor \[TKI\] such as alectinib is not allowed in any setting) 4. Measurable disease (1 or more target lesions per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) 5. Pretreatment tumor tissue Exclusion Criteria: 1. Patient's cancer has a known oncogenic driver alteration other than ALK. 2. Known allergy/hypersensitivity to excipients of neladalkib or alectinib. 3. Ongoing or recent radiotherapy as per protocol-specified timeframes prior to randomization 4. Major surgery within 4 weeks prior to randomization 5. Uncontrolled clinically relevant infection requiring systemic therapy 6. Known active tuberculosis, or active Hepatitis B or C 7. QT corrected for heart rate by Fridericia's formula (QTcF) \> 470 msec on repeated assessments 8. Clinically significant cardiovascular disease 9. Brain metastases associated with progressive neurological symptoms or requiring increasing doses of corticosteroids to control CNS disease 10. Active malignancy requiring therapy within 2 years prior to randomization

Interventions

DRUG

Neladalkib (NVL-655)

DRUG

Alectinib

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Non-small Cell Lung CancerAnaplastic Lymphoma Kinase-positive

Locations

Palo Verde Hematology Oncology

Glendale, Arizona 85304

United States

Hoag Hospital Newport Beach

Newport Beach, California 92663

United States

University of California, Irvine Health

Orange, California 92868

United States

Rocky Mountain Cancer Centers

Boulder, Colorado 80218

United States

Sylvester Comprehensive Cancer Center Miami

Miami, Florida 33136

United States

AdventHealth Cancer Institute

Orlando, Florida 32804

United States

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida 33612

United States

Winship Cancer Institute of Emory University

Atlanta, Georgia 30322

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Washington University Center for Advanced Medicine

St Louis, Missouri 63110

United States

NYU Langone's Perlmutter Cancer Center

New York, New York 10016

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Optum Medical Care, PC

Westbury, New York 11590

United States

Carolinas Medical Center

Charlotte, North Carolina 28203

United States

Duke Cancer Center

Durham, North Carolina 27710

United States

University of Cincinnati Cancer Center

Cincinnati, Ohio 45267

United States

The Ohio State University

Columbus, Ohio 43210

United States

Alliance Cancer Specialists

Sellersville, Pennsylvania 18960

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

University of Washington - Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

Compass Oncology

Vancouver, Washington 98684

United States

Sanatorio Parque S.A.

Rosario, Santa Fe Province S20000DSV

Argentina

Sanatorio Allende

Córdoba, 5000

Argentina

Centro Médico Privado CEMIC

Córdoba, X5008

Argentina

Westmead Hospital

Westmead, New South Wales 2145

Australia

Austin Health

Heidelberg, Victoria 3084

Australia

Peter MacCallum Cancer Centre

Melbourne, 3000

Australia

Wiener Gesundheitsverbund

Vienna, 1210

Austria

Cliniques Universitaires Saint-Luc

Brussels, 1200

Belgium

Antwerp University Hospital

Edegem, 2650

Belgium

UZ Leuven

Leuven, 3000

Belgium

Fundação Pio XII

Barretos, 14784

Brazil

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, 30150

Brazil

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90035

Brazil

Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul

Porto Alegre, 90610

Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base

São José do Rio Preto, 15090

Brazil

Instituto do Cancer do Estado de São Paulo ICESP

São Paulo, 01246-000

Brazil

A.C.Camargo Cancer Center

São Paulo, 01509-010

Brazil

Hospital Amaral Carvalho

São Paulo, 17210-080

Brazil

Princess Margaret Cancer Centre

Toronto, Ontario M5G 1L7

Canada

Fundacion Arturo Lopez Perez FALP

Providencia, 7500000

Chile

Centro de Oncologia de Precision de la Universidad Mayor

Santiago, 5750

Chile

Centro de Investigaciones Clinicas UC CICUC

Santiago, 8320000

Chile

Oncovida - Santiago

Santiago, 8320000

Chile

Nemocnice AGEL Nový Jičín a.s.

Nový Jičín, 74101

Czechia

Aarhus Universitetshospital

Aarhus, 8200

Denmark

Herlev and Gentofte Hospital

Herlev, 02730

Denmark

University of Southern Denmark

Odense, 5000

Denmark

Centre Hospitalier Universitaire d' Angers

Angers, 49000

France

Institut Bergonie

Bordeaux, 33000

France

Centre Francois Baclesse

Caen, 14076

France

Centre Leon Berard

Lyon, 69373

France

Hospital Nord

Marseille, 13015

France

Institut Regional du Cancer de Montpellier

Montpellier, 34298

France

Centre Hospitalier Universitaire (CHU) Nantes Hopital Nord Laennec

Nantes, 44093

France

APHP - Hôpital Tenon

Paris, 75020

France

Centre Hospitalier Universitaire (CHU) de Bordeaux

Pessac, 33604

France

Centre Hospitalier Universitaire de Toulouse - Hopital Larrey

Toulouse, 31059

France

Helios Klinikum Emil von Behring GmbH

Berlin, 14165

Germany

Klinikum Esslingen GmbH

Esslingen am Neckar, 73730

Germany

LungenClinic Grosshansdorf GmBH

Großhansdorf, D-22927

Germany

Lungenfachklinik Immenhausen

Immenhausen, 34376

Germany

MVZ Onkologie Velbert

Velbert, 42551

Germany

Henry Dunant Hospital Center

Athens, 115 26

Greece

Sotiria Thoracic Diseases Hospital of Athens

Athens, 115 27

Greece

University General Hospital of Larissa

Larissa, 411 10

Greece

Athens Medical Center

Marousi, 151 25

Greece

GENESIS General Clinic

Thessaloniki, 555 35

Greece

Queen Mary Hospital Department of Medicine

Hong Kong, 999077

Hong Kong

Queen Elizabeth Hospital

Hong Kong,

Hong Kong

Prince of Wales Hospital

Shatin,

Hong Kong

Debreceni Egyetem Klinikai Kozpont Nagyerdei Campus

Debrecen, 4032

Hungary

Matrai Gyogyintezet

Gyöngyös, 7151

Hungary

Bacs-Kiskun Varmegyei Oktatokorhaz

Kecskemét, 6000

Hungary

Azienda Ospedaliero Universitaria delle Marche

Ancona, 60126

Italy

IRCCS Istituto Tumori Giovanni Paolo II

Bari, 70124

Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

Meldola, 47014

Italy

Istituto Clinico Humanitas

Milan, 20089

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133

Italy

Istituto Europeo di Oncologia

Milan, 20141

Italy

Fondazione IRCCS San Gerardo dei Tintori

Monza, 20900

Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126

Italy

AUSL Della Romagna - Ospedale Santa Maria delle Croci

Ravenna, 48121

Italy

Istituti Fisioterapici Ospitalieri - IRCCS Istituto Nazionale Tumori Regina Elena

Roma, 00144

Italy

ASL Taranto Ospedale S. G. Moscati

Statte, 74010

Italy

Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia

Torino, 10060

Italy

Kyushu University Hospital

Fukuoka, Fukuoka 812-8582

Japan

Aichi Cancer Center

Chikusa, 464-8681

Japan

Shizuoka Cancer Center

Nagaizumi-chō, 411-0934

Japan

Okayama University Hospital

Okayama, 700-8558

Japan

Osaka International Cancer Institute

Osaka, 541-8567

Japan

Kindai University Hospital

Sakai, 590-0197

Japan

National Cancer Center Hospital

Tokyo, 1040045

Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Tokyo, 135-8550

Japan

Wakayama Medical University Hospital

Wakayama, 641-0012

Japan

Kanagawa Cancer Center

Yokohama, 241-8515

Japan

Hospital Kuala Lumpur

Kuala Lumpur, Kuala Lumpur 50586

Malaysia

Hospital Pulau Pinang

George Town, Pulau Pinang 10450

Malaysia

Institut Kanser Negara

Putrajaya, Putrajaya 62250

Malaysia

Beacon International Specialist Centre

Petaling Jaya, Selangor 46050

Malaysia

Hospital Umum Sarawak

Kuching, 93586

Malaysia

Sunway Medical Centre

Subang Jaya, 47500

Malaysia

Health Pharma Professional Research S.A de C.V.

Mexico City, 03100

Mexico

Centro Oncológico Personalizado

Mexico City, 06760

Mexico

Hospital Universitario Dr. Jose Eleuterio González

Monterrey, 64660

Mexico

Centro de Investigacion Clinica Chapultepec S.A. de C.V.

Morelia, 58260

Mexico

Oncologia Integral Satelite S. A. de C. V.

Naucalpan, 53100

Mexico

Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX

Netherlands

Radboud University Medical Center

Nijmegen, 6525 GA

Netherlands

University Medical Center Utrecht

Utrecht, 3584

Netherlands

Szpital Specjalistyczny w Brzozowie

Brzozów, 36-200

Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952

Poland

Zanamed Medical Clinic Sp. z o.o.

Lublin, 20-601

Poland

One Day Med

Szczecin, 70-419

Poland

Hospital de Cascais

Alcabideche, 2755-009

Portugal

Fundacao Champalimaud

Lisbon, 1400-038

Portugal

CUF Porto Hospital

Porto, 4100-180

Portugal

Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.

Porto, 4200-072

Portugal

National Cancer Centre Singapore

Singapore, 168583

Singapore

Tan Tock Seng Hospital

Singapore, 308433

Singapore

Chungbuk National University Hospital

Cheongju-si, 28644

South Korea

Center for Lung Cancer, National Cancer Center

Goyang-si, 10408

South Korea

Gachon University Gil Medical Center

Incheon, 21565

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital Yonsei Cancer Center

Seoul, 03722

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Complejo Hospitalario Universitario a Coruña

A Coruña, 15006

Spain

ICO Badalona H.U. Germans Trias i Pujol

Badalona, 08916

Spain

UOMi Cancer Center

Barcelona, 08017

Spain

Hospital Universitari de Girona Dr Josep Trueta

Girona, 17007

Spain

Hospital General Universitario Gregorio Marañon

Madrid, 28007

Spain

Hospital Universitario Ramon y Cajal

Madrid, 28034

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Regional Universitario de Malaga

Málaga, 29010

Spain

Hospital Universitario Virgen Macarena

Seville, 41009

Spain

Hospital Universitario Virgen del Rocio

Seville, 41013

Spain

Luzerner Kantonsspital

Lucerne, 6004

Switzerland

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756

Taiwan

Chung Shan Medical University

Taichung, 40201

Taiwan

National Cheng Kung University Hospital

Tainan, 70403

Taiwan

National Taiwan University Hospital

Taipei,

Taiwan

Phramongkutklao Hospital

Bangkok, 10400

Thailand

Ramathibodi Hospital, Mahidol University

Bangkok, 10400

Thailand

Siriraj Hospital Mahidol University

Bangkok, 10700

Thailand

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200

Thailand

Rajavithi Hospital

Din Daeng, 10400

Thailand

HRH Princess Maha Chakri Sirindhorn Medical Center

Ongkharak, 26120

Thailand

Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital

Cambridge, NG5 1PB

United Kingdom

Royal Surrey County Hospital

Guildford, GU2 7XX

United Kingdom

Royal Free London NHS Foundation Trust

Hampstead, NW3 2QG

United Kingdom

Guy's Cancer Centre NHS Foundation Trust

London, SE1 9RT

United Kingdom

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ

United Kingdom

Maidstone Hospital

Maidstone, ME16 9QQ

United Kingdom

The Christie NHS Foundation Trust

Manchester, M20 4BX

United Kingdom

Nottingham City Hospital

Nottingham, NG5 1PB

United Kingdom