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

NCT05384626 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NVL-655-01
• Study Type: interventional
• Target: 840
• Locations: 15 countries
• Sites: 74

Brief 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.

Conditions

Locally Advanced Solid Tumor; Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Dose limiting toxicities (DLTs) (Phase 1)

  Define the dose limiting toxicities (DLTs)

  Within the first 21 days of the first neladalkib (NVL-655) dose

• Recommended Phase 2 Dose (RP2D) (Phase 1)

  To determine the RP2D

  Within 21 days of last patient dosed during escalation

• Objective Response Rate (ORR) (Phase 2)

  To determine ORR as assessed by BICR

  2-3 years after first patient dosed.

• Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)

  Incidence and severity of treatment-emergent adverse events (TEAEs)

  Approximately 3 years

Secondary Outcomes (18)

• Maximum plasma concentration, (Cmax) of neladalkib (NVL-655)

  Pre-dose and up to 24 hours post-dose

• Plasma concentration at the end of the dosing interval (Ctau) of neladalkib (NVL-655)

  Pre-dose and up to 24 hours post-dose

• Average plasma concentration (Cavg) of neladalkib (NVL-655)

  Pre-dose and up to 24 hours post-dose

• Time of maximum concentration (Tmax) of neladalkib (NVL-655)

  Pre-dose and up to 24 hours post-dose

• Area under the curve at the end of the dosing interval (AUCtau) of neladalkib (NVL-655)

  Pre-dose and up to 24 hours post-dose

Study Arms (7)

Phase 1 dose escalation

EXPERIMENTAL

Neladalkib (NVL-655) oral daily dosing

Drug: Neladalkib (NVL-655)

Cohort 2a

EXPERIMENTAL

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.

Drug: Neladalkib (NVL-655)

Cohort 2b

EXPERIMENTAL

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.

Drug: Neladalkib (NVL-655)

Cohort 2c

EXPERIMENTAL

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.

Drug: Neladalkib (NVL-655)

Cohort 2d

EXPERIMENTAL

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.

Drug: Neladalkib (NVL-655)

Cohort 2e

EXPERIMENTAL

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.

Drug: Neladalkib (NVL-655)

Cohort 2f

EXPERIMENTAL

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.

Drug: Neladalkib (NVL-655)

Interventions

Neladalkib (NVL-655) DRUG

Oral Tablet of Neladalkib (NVL-655)

Cohort 2a; Cohort 2b; Cohort 2c; Cohort 2d; Cohort 2e; Cohort 2f; Phase 1 dose escalation

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nuvalent Inc.: lead

Study Sites (74)

University of California Irvine Medical Center

Orange, California, 92868, United States

RECRUITING

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Stanford Cancer Institute

Stanford, California, 94305, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

University of Miami; Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

John Hopkins University

Baltimore, Maryland, 21224, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

RECRUITING

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, 63310, United States

RECRUITING

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27705, United States

RECRUITING

OSU Brain & Spine Hospital

Columbus, Ohio, 43210, United States

RECRUITING

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Sarah Cannon

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Universitair Ziekenhuis Antwerpen (UZA)

Antwerp, 2650, Belgium

RECRUITING

Universitaire Ziekenhuizen Leuven Campus Gastthuisberg

Leuven, 3000, Belgium

RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

BC Cancer Center

Vancouver, British Columbia, VZ 4E6, Canada

RECRUITING

The Ottawa Hospital Cancer Center

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 0A3, Canada

RECRUITING

Centre Leon Berard

Lyon, 69373, France

RECRUITING

Chu De Nantes

Nantes, 44093, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

Institute Gustave Roussy

Villejuif, 94805, France

RECRUITING

Universitatsklinikum Koln - University Hospital Cologne

Cologne, 50937, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

RECRUITING

LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927, Germany

RECRUITING

Universkitatsklinikum Heidelberg - University Hospital Heidelberg

Heidelberg, 69126, Germany

RECRUITING

Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto

Ancona, 60126, Italy

RECRUITING

IRCCS Istituto Tumori "G. Paolo II"

Bari, 70124, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Instituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Instituto Oncologico Veneto

Padua, 35128, Italy

RECRUITING

Ospedale Santa Maria delle Croci

Ravenna, 48100, Italy

RECRUITING

Regina Elena Institute for Cancer Research

Rome, 00144, Italy

RECRUITING

Kanagawa Cancer Center

Kanagawa, 2418515, Japan

RECRUITING

Okayama University Hospital

Okayama, 7008558, Japan

RECRUITING

Kindai University Hospital

Osaka, 5898511, Japan

RECRUITING

Shizuoka Cancer Center

Shizuoka, 4118777, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, 1040051, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Tokyo, 1358550, Japan

RECRUITING

Wakayama Medical University Hospital

Wakayama, 6418510, Japan

RECRUITING

The Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

RECRUITING

University Medical Center Groningen (UMCG)

Groningen, 9713 GZ, Netherlands

RECRUITING

National University Hospital

Singapore, Singapore, 119074, Singapore

RECRUITING

National Cancer Centre Singapore

Singapore, Singapore, 168583, Singapore

RECRUITING

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Complejo Hospitalario Universitario de A Coruna

A Coruña, 15006, Spain

RECRUITING

UOMI Cancer Center

Barcelona, 08017, Spain

RECRUITING

Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, 28009, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Istituto Oncologico Svizzera Italiana

Bellinzona, 6500, Switzerland

RECRUITING

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

RECRUITING

Chung-Shan Medical University Hospital

Taichung, 402306, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

Edinburgh Cancer Centre

Edinburgh, EH4 2XU, United Kingdom

RECRUITING

The Royal Marsden - Chelsea

London, SM2 5PT, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Viola Zhu, MD, PHD

  Nuvalent Inc.

  STUDY DIRECTOR

Central Study Contacts

Nuvalent Clinical Trial

CONTACT

857-357-7000; clinicaltrials@nuvalent.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 20, 2022
• Study Start: June 9, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: October 30, 2025

Record last verified: 2025-10

Locations

AU (3); DE (4); BE (2); US (21); IT (7); NL (2); GB (4); CA (4); KR (4); JP (7); SG (2); FR (4); TW (3); ES (5); CH (2)