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Locally Advanced Solid TumorPhase 1/2NCT05384626

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 testing Neladalkib (NVL-655), Midazolam and Repaglinide in people with Locally Advanced Solid Tumor and Metastatic Solid Tumor, run by Nuvalent Inc. at 74 sites in 15 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Neladalkib (NVL-655), Midazolam and Repaglinide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
840 participants
Where
74 sitesin 15 countries
Study dates
9 Jun 2022to Jan 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing >40 kg. DDI sub-study Cohorts G and H only: age 18-60 years, inclusive
  • 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.
  • DDI sub-study cohorts: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
Show all 9Show fewer
  • DDI sub-study cohorts: Must have previously received ≥1 ALK TKI; no prior investigational agents targeting ALK; any number of prior chemotherapy and/or immunotherapy
  • 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

Who cannot join

  • 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.

Trial locations and contacts

74 sites in 15 countries. Contact the study team or a site near you to ask about taking part.

Nuvalent Clinical Trial contact

857-357-7000

clinicaltrials@nuvalent.com

74 sites in 15 countries

United States21 sites, 20 recruiting

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322

    Ticiana Leal, MD

    Recruiting

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

    Ross Camidge, MD, PhD

    Recruiting

  • John Hopkins University

    Baltimore, Maryland, 21224

    Vincent Lam, MD

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Jessica Lin, MD

    Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Alice Shaw, MD

    Recruiting

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

    Marina Garassino, MD

    Recruiting

  • OSU Brain & Spine Hospital

    Columbus, Ohio, 43210

    Logan Roof, MD, MSCR

    Recruiting

  • Henry Ford Cancer Institute

    Detroit, Michigan, 48202

    Bindu Potugari, MD

    Recruiting

  • Duke University Medical Center

    Durham, North Carolina, 27705

    Thomas Stinchcombe, MD

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Active, not recruiting

  • University of Miami; Sylvester Cancer Center

    Miami, Florida, 33136

    Gilberto de Lima Lopes, MD

    Recruiting

  • Sarah Cannon

    Nashville, Tennessee, 37203

    Melissa Johnson, MD

    Recruiting

  • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

    New York, New York, 10016

    Elaine Shum, MD

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Alexander Drilon, MD

    Recruiting

  • University of California Irvine Medical Center

    Orange, California, 92868

    Misako Nagasaka, MD

    Recruiting

  • University of Pennsylvania, Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

    Charu Aggarwal, MD

    Recruiting

  • University of California, Davis Comprehensive Cancer Center

    Sacramento, California, 95817

    Jonathan Riess, MD

    Recruiting

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

    Christina Baik, MD, MPH

    Recruiting

  • Washington University School of Medicine Siteman Cancer Center

    St Louis, Missouri, 63310

    Saiama Waqar, MD

    Recruiting

  • Stanford Cancer Institute

    Stanford, California, 94305

    Joel Neal, MD, PhD

    Recruiting

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

    Joshua Reuss, MD

    Recruiting

Other trials in United States

Italy7 sites, 7 recruiting

  • Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto

    Ancona, 60126

    Rossana Berardi, MD

    Recruiting

  • IRCCS Istituto Tumori "G. Paolo II"

    Bari, 70124

    Domenico Galetta, MD

    Recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

    Sara Cresta, MD

    Recruiting

  • Instituto Europeo di Oncologia

    Milan, 20141

    Gianluca Spitaleri, MD

    Recruiting

  • Instituto Oncologico Veneto

    Padova, 35128

    Giulia Pasello, MD

    Recruiting

  • Ospedale Santa Maria delle Croci

    Ravenna, 48100

    Chiara Bennati, MD

    Recruiting

  • Regina Elena Institute for Cancer Research

    Rome, 00144

    Lorenza Landi, MD

    Recruiting

Other trials in Italy

Japan7 sites, 7 recruiting

  • Kanagawa Cancer Center

    Kanagawa, 2418515

    Tetsuro Kondo, MD

    Recruiting

  • Okayama University Hospital

    Okayama, 7008558

    Kiichiro Ninomiya, MD

    Recruiting

  • Kindai University Hospital

    Osaka, 5898511

    Junko Tanizaki, MD

    Recruiting

  • Shizuoka Cancer Center

    Shizuoka, 4118777

    Ryo Ko, MD PhD

    Recruiting

  • National Cancer Center Hospital

    Tokyo, 1040051

    Tatsuya Yoshida, MD

    Recruiting

  • Cancer Institute Hospital of JFCR

    Tokyo, 1358550

    Ryo Ariyasu, MD

    Recruiting

  • Wakayama Medical University Hospital

    Wakayama, 6418510

    Hiroaki Akamatsu, MD, PhD

    Recruiting

Other trials in Japan

Spain5 sites, 5 recruiting

  • Complejo Hospitalario Universitario de A Coruna

    A Coruña, 15006

    Maria Campelo, MD

    Recruiting

  • UOMI Cancer Center

    Barcelona, 08017

    Santiago Viteri Ramirez, MD PhD

    Recruiting

  • Vall d'Hebron

    Barcelona, 08035

    Enriqueta Felip, Md, PhD

    Recruiting

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28009

    Antonio Calles, MD

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Luis Paz Ares, MD, PhD

    Recruiting

Other trials in Spain

Canada4 sites, 4 recruiting

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

    Quincy Siu Chung Chu, MD

    Recruiting

  • The Ottawa Hospital Cancer Center

    Ottawa, Ontario, K1H 8L6

    Garth Nicholas, MD

    Recruiting

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 0A3

    Geoffrey Liu, M.D.

    Recruiting

  • BC Cancer Center

    Vancouver, British Columbia, VZ 4E6

    Jamie Feng, MD

    Recruiting

Other trials in Canada

France4 sites, 4 recruiting

  • Centre Leon Berard

    Lyon, 69373

    Aurelie Swalduz, MD

    Recruiting

  • Chu De Nantes

    Nantes, 44093

    Elvire Pons-Tostivint, MD, PhD

    Recruiting

  • Institut Claudius Regaud

    Toulouse, 31059

    Julien Mazieres, MD, PhD

    Recruiting

  • Institute Gustave Roussy

    Villejuif, 94805

    Benjamin Besse, MD, PhD

    Recruiting

Other trials in France

Germany4 sites, 4 recruiting

  • Universitatsklinikum Koln - University Hospital Cologne

    Cologne, 50937

    Dr med Sebastian Michels

    Recruiting

  • Universitätsklinikum Frankfurt

    Frankfurt, 60590

    Martin Sebastian, MD

    Recruiting

  • LungenClinic Grosshansdorf GmbH

    Großhansdorf, 22927

    Prof Dr Martin Reck

    Recruiting

  • Universkitatsklinikum Heidelberg - University Hospital Heidelberg

    Heidelberg, 69126

    Prof Dr med Petros Christopoulos

    Recruiting

Other trials in Germany

South Korea4 sites, 4 recruiting

  • National Cancer Center

    Goyang-si, Gyeonggi-do, 10408

    Ji-Youn Han, MD

    Recruiting

  • Seoul National University Hospital

    Seoul, 03080

    Dong-wan Kim, MD

    Recruiting

  • Severance Hospital Yonsei University Health System

    Seoul, 03722

    Byoung Chul Cho, MD

    Recruiting

  • Samsung Medical Center

    Seoul, 06351

    Myung-Ju Ahn, MD

    Recruiting

Other trials in South Korea

United Kingdom4 sites, 4 recruiting

  • Edinburgh Cancer Centre

    Edinburgh, EH4 2XU

    Colin Barrie, MD

    Recruiting

  • The Royal Marsden - Chelsea

    London, SM2 5PT

    Sanjay Popat MD

    Recruiting

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

    Matthew Krebs, MB ChB PhD

    Recruiting

  • Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

    Sanjay Popat MD

    Recruiting

Other trials in United Kingdom

Australia3 sites, 3 recruiting

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

    Benjamin Solomon, MD, PhD

    Recruiting

  • Royal North Shore Hospital

    Sydney, New South Wales, 2065

    Malinda Itchins, MBBS PhD

    Recruiting

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

    Kenneth O'Byrne, MD

    Recruiting

Other trials in Australia

Taiwan3 sites, 3 recruiting

  • Chung-Shan Medical University Hospital

    Taichung, 402306

    Gee-Chen Chang, MD

    Recruiting

  • National Cheng Kung University Hospital

    Tainan, 70403

    Chien-Chung Lin, MD

    Recruiting

  • National Taiwan University Hospital

    Taipei, 10002

    Josh Lin, MD

    Recruiting

Other trials in Taiwan

Belgium2 sites, 2 recruiting

  • Universitair Ziekenhuis Antwerpen (UZA)

    Antwerp, 2650

    Reinier Wener, MD

    Recruiting

  • Universitaire Ziekenhuizen Leuven Campus Gastthuisberg

    Leuven, 3000

    Christophe Dooms, MD

    Recruiting

Other trials in Belgium

Netherlands2 sites, 2 recruiting

  • The Netherlands Cancer Institute

    Amsterdam, 1066 CX

    Adrianus Joop de Langen, MD

    Recruiting

  • University Medical Center Groningen (UMCG)

    Groningen, 9713 GZ

    AJ Van Der Wekken, MD

    Recruiting

Other trials in Netherlands

Singapore2 sites, 2 recruiting

  • National University Hospital

    Singapore, Singapore, 119074

    Ross Soo, MD

    Recruiting

  • National Cancer Centre Singapore

    Singapore, Singapore, 168583

    Aaron Tan, MD

    Recruiting

Other trials in Singapore

Switzerland2 sites, 2 recruiting

  • Istituto Oncologico Svizzera Italiana

    Bellinzona, 6500

    Patrizia Froesch, MD

    Recruiting

  • Luzerner Kantonsspital

    Lucerne, 6000

    Anna Allemann, MD

    Recruiting

Other trials in Switzerland

About this study

Official title: 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)

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.

Read more

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.

A drug-drug interaction (DDI) sub-study will determine the effect of neladalkib on the pharmacokinetics of midazolam and repaglinide, as well as the effect of itraconazole on the pharmacokinetics of neladalkib, in patients with advanced ALK-positive NSCLC

Read the detailed description

In Phase 2, study patients will be enrolled into 6 distinct cohorts:

  • Cohort 2a: 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.
  • Cohort 2b: 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.
  • Cohort 2c: 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.
  • Cohort 2d: 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.
  • Cohort 2e: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
  • Cohort 2f: 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.

In the DDI sub-study, study patients will be enrolled into 2 distinct cohorts:

  • Cohort G (DDI sub-study with midazolam and repaglinide): Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI.
  • Cohort H (DDI sub-study with itraconazole): Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI.
Being tested
Neladalkib (NVL-655), Midazolam, Repaglinide, Itraconazole
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Neladalkib (NVL-655)Drug

    Oral Tablet of Neladalkib (NVL-655)

  • MidazolamDrug

    Oral Solution of Midazolam

  • RepaglinideDrug

    Oral Tablet of Repaglinide

  • ItraconazoleDrug

    Oral Solution of Itraconazole

Study groups in NCT05384626
Study groupRoleWhat they receive
Phase 1 dose escalationExperimentalNeladalkib (NVL-655) oral daily dosing
Receives: Drug: Neladalkib (NVL-655)
Cohort 2aExperimentalPatients 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.
Receives: Drug: Neladalkib (NVL-655)
Cohort 2bExperimentalPatients 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.
Receives: Drug: Neladalkib (NVL-655)
Cohort 2cExperimentalPatients 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.
Receives: Drug: Neladalkib (NVL-655)
Cohort 2dExperimentalPatients 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.
Receives: Drug: Neladalkib (NVL-655)
Cohort 2eExperimentalPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
Receives: Drug: Neladalkib (NVL-655)
Cohort 2fExperimentalPatients 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.
Receives: Drug: Neladalkib (NVL-655)
Cohort G (DDI sub-study)ExperimentalPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI
Receives: Drug: Neladalkib (NVL-655); Drug: Midazolam; Drug: Repaglinide
Cohort H (DDI sub-study)ExperimentalPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI
Receives: Drug: Neladalkib (NVL-655); Drug: Itraconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicities (DLTs) (Phase 1)

    Define the dose limiting toxicities (DLTs)

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

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

    To determine the RP2D

    Measured: Within 21 days of last patient dosed during escalation

  3. Objective Response Rate (ORR) (Phase 2)

    To determine ORR as assessed by BICR

    Measured: 2-3 years after first patient dosed.

  4. 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)

    Measured: Approximately 3 years

  5. Area under the curve of repaglinide (Phase 2 DDI sub-study)

    To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of repaglinide

    Measured: Pre-dose and up to 24 hours post-dose

  6. Area under the curve of midazolam (Phase 2 DDI sub-study)

    To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of midazolam

    Measured: Pre-dose and up to 24 hours post-dose

  7. Area under the curve of neladalkib (NVL-655) (Phase 2 DDI sub-study)

    To determine the effect of itraconazole on the single oral dose PK of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

Secondary outcomes (20)

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

    To determine the maximum plasma concentration (Cmax) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

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

    To determine the plasma concentration at the end of the dosing interval (Ctau) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

  3. Average plasma concentration (Cavg) of neladalkib (NVL-655)

    To determine the average plasma concentration (Cavg) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

  4. Time of maximum concentration (Tmax) of neladalkib (NVL-655)

    To determine the time of maximum concentration (Tmax) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

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

    To determine the area under the curve at the end of the dosing interval (AUCtau) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

  6. Area under the curve from time 0 to 24 (AUC0-24) of neladalkib (NVL-655)

    To determine the area under the curve from time 0 to 24 (AUC0-24) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

  7. Area under the curve from time 0 to infinity (AUCinf) of neladalkib (NVL-655)

    To determine the area under the curve from time 0 to infinity (AUCinf) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

  8. Oral clearance (CL/F) of neladalkib (NVL-655)

    To determine the oral clearance (CL/F) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

  9. Volume of distribution (Vz/F) of neladalkib (NVL-655)

    To determine the volume of distribution (Vz/F) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

  10. Half-life (t1/2) of neladalkib (NVL-655)

    To determine the half-life (t1/2) of neladalkib (NVL-655)

    Measured: Pre-dose and up to 24 hours post-dose

  11. Objective response rate (ORR) (Phase 1)

    Determine ORR as assessed by Investigator

    Measured: 2-3 years after first patient dosed

  12. Duration of response (DOR)

    Determine DOR of neladalkib (NVL-655) until radiographic disease progression or death

    Measured: 2-3 years after first patient dosed

  13. Clinical benefit rate (CBR)

    Determine CBR of neladalkib (NVL-655)

    Measured: 2-3 years after first patient dosed

  14. Time to response

    Determine time to response of neladalkib (NVL-655)

    Measured: Approximately 3 years

  15. Progression-free survival (PFS)

    Determine PFS of neladalkib (NVL-655) until radiographic disease progression or death

    Measured: 2-3 years after first patient dosed

  16. Overall survival (OS) (Phase 2)

    Determine OS

    Measured: Approximately 3 years

  17. Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2)

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

    Measured: Approximately 3 years

  18. Quality of life assessment

    Measure the quality of life in patients with cancer and/or lung cancer.

    Measured: 2-3 years after first patient dosed

  19. Incidence and severity of AEs and incidence of abnormalities across laboratory values, ECGs, vital signs, and physical examinations (Phase 2 DDI-sub-study)

    Assess the safety and tolerability of neladalkib (NVL-655) when co-administered with repaglinide or midazolam

    Measured: Up to 3 months after last dose

  20. Incidence and severity of AEs and incidence of abnormalities across laboratory values, ECGs, vital signs, and physical examinations (Phase 2 DDI-sub-study)

    Assess the safety and tolerability of neladalkib (NVL-655) when co-administered with itraconazole

    Measured: Up to 3 months after last dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2022
  2. Study start9 Jun 2022
  3. Primary completionDec 2027 (estimated)
  4. Study completionJan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
840 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05384626
Sponsor's protocol ID
NVL-655-01
Status last verified
Nov 2026
First submitted
17 May 2022
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Neladalkib (NVL-655), Midazolam and Repaglinide in people with Locally Advanced Solid Tumor and Metastatic Solid Tumor, run by Nuvalent Inc. at 74 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 74 sites in United States, Italy, Japan, Spain, Canada and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nuvalent Clinical Trial (857-357-7000, clinicaltrials@nuvalent.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (DLTs) (Phase 1) (time frame: Within the first 21 days of the first neladalkib (NVL-655) dose). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05384626.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.

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