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

NCT ID: NCT06765109

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

450 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-17

Study Completion Date

2029-12-31

Brief Summary

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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

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

Conditions

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Non-small Cell Lung Cancer Anaplastic Lymphoma Kinase-positive

Keywords

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NSCLC Lung cancer Lung neoplasms Lung diseases ALK positive NSCLC TKI naive ALK TKI naive Treatment naive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Neladalkib (NVL-655)

150mg taken orally once daily (QD)

Group Type EXPERIMENTAL

Neladalkib (NVL-655)

Intervention Type DRUG

Oral tablet of Neladalkib (NVL-655)

Alectinib

600mg taken orally twice daily (BID)

Group Type ACTIVE_COMPARATOR

Alectinib

Intervention Type DRUG

Oral capsule of alectinib

Interventions

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Neladalkib (NVL-655)

Oral tablet of Neladalkib (NVL-655)

Intervention Type DRUG

Alectinib

Oral capsule of alectinib

Intervention Type DRUG

Other Intervention Names

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Alecensa

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nuvalent Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Viola Zhu, MD, PhD

Role: STUDY_DIRECTOR

Nuvalent Inc.

Locations

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Palo Verde Hematology Oncology

Glendale, Arizona, United States

Site Status RECRUITING

University of California, Irvine Health

Orange, California, United States

Site Status RECRUITING

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Site Status RECRUITING

Sylvester Comprehensive Cancer Center Miami

Miami, Florida, United States

Site Status RECRUITING

AdventHealth Cancer Institute

Orlando, Florida, United States

Site Status RECRUITING

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

Washington University Center for Advanced Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Clinical Research Alliance Inc.

New Hyde Park, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Duke Cancer Center

Durham, North Carolina, United States

Site Status RECRUITING

University of Cincinnati Cancer Center

Cincinnati, Ohio, United States

Site Status RECRUITING

The Ohio State University

Columbus, Ohio, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status RECRUITING

Sanatorio Parque S.A.

Rosario, Santa Fe Province, Argentina

Site Status RECRUITING

Westmead Hospital

Westmead, New South Wales, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status RECRUITING

Antwerp University Hospital

Edegem, , Belgium

Site Status RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status RECRUITING

Nemocnice AGEL Nový Jičín a.s.

Nový Jičín, , Czechia

Site Status RECRUITING

Herlev and Gentofte Hospital

Herlev, , Denmark

Site Status RECRUITING

University of Southern Denmark

Odense, , Denmark

Site Status RECRUITING

Centre Hospitalier Universitaire d' Angers

Angers, , France

Site Status RECRUITING

Institut Bergonie

Bordeaux, , France

Site Status RECRUITING

Centre Francois Baclesse

Caen, , France

Site Status RECRUITING

Centre Leon Berard

Lyon, , France

Site Status RECRUITING

Hospital Nord

Marseille, , France

Site Status RECRUITING

Institut Regional du Cancer de Montpellier

Montpellier, , France

Site Status RECRUITING

Centre Hospitalier Universitaire (CHU) Nantes Hopital Nord Laennec

Nantes, , France

Site Status RECRUITING

Centre Hospitalier Universitaire (CHU) de Bordeaux

Pessac, , France

Site Status RECRUITING

Centre Hospitalier Universitaire de Toulouse - Hopital Larrey

Toulouse, , France

Site Status RECRUITING

Klinikum Esslingen GmbH

Esslingen am Neckar, , Germany

Site Status RECRUITING

LungenClinic Grosshansdorf GmBH

Großhansdorf, , Germany

Site Status RECRUITING

Lungenfachklinik Immenhausen

Immenhausen, , Germany

Site Status RECRUITING

Henry Dunant Hospital Center

Athens, , Greece

Site Status RECRUITING

Sotiria Thoracic Diseases Hospital of Athens

Athens, , Greece

Site Status RECRUITING

University General Hospital of Larissa

Larissa, , Greece

Site Status RECRUITING

Athens Medical Center

Marousi, , Greece

Site Status RECRUITING

Bioclinic Thessaloniki

Thessaloniki, , Greece

Site Status RECRUITING

Queen Mary Hospital Department of Medicine

Hong Kong, , Hong Kong

Site Status RECRUITING

Matrai Gyogyintezet

Gyöngyös, , Hungary

Site Status RECRUITING

Istituto Clinico Humanitas

Milan, , Italy

Site Status RECRUITING

AUSL Della Romagna - Ospedale Santa Maria delle Croci

Ravenna, , Italy

Site Status RECRUITING

Istituti Fisioterapici Ospitalieri - IRCCS Istituto Nazionale Tumori Regina Elena

Roma, , Italy

Site Status RECRUITING

Kyushu University Hospital

Fukuoka, Fukuoka, Japan

Site Status RECRUITING

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Tokyo, , Japan

Site Status RECRUITING

Kanagawa Cancer Center

Yokohama, , Japan

Site Status RECRUITING

Hospital Kuala Lumpur

Kuala Lumpur, Kuala Lumpur, Malaysia

Site Status RECRUITING

Hospital Pulau Pinang

George Town, Pulau Pinang, Malaysia

Site Status RECRUITING

Institut Kanser Negara

Putrajaya, Putrajaya, Malaysia

Site Status RECRUITING

Beacon International Specialist Centre

Petaling Jaya, Selangor, Malaysia

Site Status RECRUITING

Hospital Umum Sarawak

Kuching, , Malaysia

Site Status RECRUITING

Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Site Status RECRUITING

Szpital Specjalistyczny w Brzozowie

Brzozów, , Poland

Site Status RECRUITING

Zanamed Medical Clinic Sp. z o.o.

Lublin, , Poland

Site Status RECRUITING

One Day Med

Szczecin, , Poland

Site Status RECRUITING

Hospital de Cascais

Alcabideche, , Portugal

Site Status RECRUITING

Fundacao Champalimaud

Lisbon, , Portugal

Site Status RECRUITING

CUF Porto Hospital

Porto, , Portugal

Site Status RECRUITING

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

Porto, , Portugal

Site Status RECRUITING

National Cancer Centre Singapore

Singapore, , Singapore

Site Status RECRUITING

Tan Tock Seng Hospital

Singapore, , Singapore

Site Status RECRUITING

Chungbuk National University Hospital

Cheongju-si, , South Korea

Site Status RECRUITING

Center for Lung Cancer, National Cancer Center

Goyang-si, , South Korea

Site Status RECRUITING

Gachon University Gil Medical Center

Incheon, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital Yonsei Cancer Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Complejo Hospitalario Universitario a Coruña

A Coruña, , Spain

Site Status RECRUITING

UOMi Cancer Center

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

Chung Shan Medical University

Taichung, , Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status RECRUITING

Royal Free London NHS Foundation Trust

Hampstead, , United Kingdom

Site Status RECRUITING

Guy's Cancer Centre NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Maidstone Hospital

Maidstone, , United Kingdom

Site Status RECRUITING

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status RECRUITING

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Australia Belgium Czechia Denmark France Germany Greece Hong Kong Hungary Italy Japan Malaysia Netherlands Poland Portugal Singapore South Korea Spain Taiwan United Kingdom

Central Contacts

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Nuvalent Clinical Trials

Role: CONTACT

Phone: 857-357-7000

Email: [email protected]

Other Identifiers

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NVL-655-04

Identifier Type: -

Identifier Source: org_study_id

2024-517553-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id