Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLC
ALKAZAR
A Phase 3 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 Compared to Alectinib in First-Line Treatment of Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer (ALKAZAR)
2 other identifiers
interventional
450
27 countries
148
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 nonsmall-cell-lung-cancer
Started Jul 2025
148 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 8, 2024
CompletedFirst Posted
Study publicly available on registry
January 9, 2025
CompletedStudy Start
First participant enrolled
July 17, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2029
May 5, 2026
March 1, 2026
4.4 years
November 8, 2024
April 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS) per blinded independent central review (BICR)
Time from randomization to BICR-assessed radiographic disease progression or death
Up to 5 years after first patient dosed
Secondary Outcomes (12)
Overall survival (OS)
Up to 5 years after first patient dosed
Progression-free survival (PFS) per investigator assessment
Up to 5 years after first patient dosed
Time to intracranial progression per BICR
Up to 5 years after first patient dosed
Intracranial objective response rate (IC-ORR)
Up to 5 years after first patient dosed
Intracranial duration of response (IC-DOR)
Up to 5 years after first patient dosed
- +7 more secondary outcomes
Study Arms (2)
Neladalkib (NVL-655)
EXPERIMENTAL150mg taken orally once daily (QD)
Alectinib
ACTIVE COMPARATOR600mg taken orally twice daily (BID)
Interventions
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed locally advanced (not amenable for multimodality treatment) or metastatic Non-small Cell Lung Cancer (NSCLC)
- Documented Anaplastic Lymphoma Kinase (ALK) rearrangement via testing of tissue or blood
- 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)
- Measurable disease (1 or more target lesions per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1)
- Pretreatment tumor tissue
You may not qualify if:
- Patient's cancer has a known oncogenic driver alteration other than ALK.
- Known allergy/hypersensitivity to excipients of neladalkib or alectinib.
- Ongoing or recent radiotherapy as per protocol-specified timeframes prior to randomization
- Major surgery within 4 weeks prior to randomization
- Uncontrolled clinically relevant infection requiring systemic therapy
- Known active tuberculosis, or active Hepatitis B or C
- QT corrected for heart rate by Fridericia's formula (QTcF) \> 470 msec on repeated assessments
- Clinically significant cardiovascular disease
- Brain metastases associated with progressive neurological symptoms or requiring increasing doses of corticosteroids to control CNS disease
- Active malignancy requiring therapy within 2 years prior to randomization
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Nuvalent Inc.lead
Study Sites (149)
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
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
Sanatorio Parque S.A.
Rosario, Santa Fe Province, S20000DSV, Argentina
Sanatorio Allende
Córdoba, 5000, 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
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 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
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
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
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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Kelly Curtis, MD
Nuvalent Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
November 8, 2024
First Posted
January 9, 2025
Study Start
July 17, 2025
Primary Completion (Estimated)
December 1, 2029
Study Completion (Estimated)
December 1, 2029
Last Updated
May 5, 2026
Record last verified: 2026-03