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 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.

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

Study Overview

• Status: Recruiting
• Conditions: Metastatic Solid Tumor; Locally Advanced Solid Tumor
• Intervention / Treatment: Drug: Neladalkib (NVL-655); Drug: Midazolam; Drug: Repaglinide; Drug: Itraconazole

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.

• Study Type: Interventional
• Enrollment (Estimated): 840
• Phase: Phase 2; Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Nuvalent Clinical Trial; Phone Number: 857-357-7000; Email: clinicaltrials@nuvalent.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2065
      • Recruiting
      • Royal North Shore Hospital
      • Principal Investigator: Malinda Itchins, MBBS PhD
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital
      • Principal Investigator: Kenneth O'Byrne, MD
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
      • Principal Investigator: Benjamin Solomon, MD, PhD
• Belgium
  • Antwerp, Belgium, 2650
    • Recruiting
    • Universitair Ziekenhuis Antwerpen (UZA)
    • Principal Investigator: Reinier Wener, MD
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitaire Ziekenhuizen Leuven Campus Gastthuisberg
    • Principal Investigator: Christophe Dooms, MD
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute
      • Principal Investigator: Quincy Siu Chung Chu, MD
  • British Columbia
    • Vancouver, British Columbia, Canada, VZ 4E6
      • Recruiting
      • BC Cancer Center
      • Principal Investigator: Barbara Melosky, MD
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital Cancer Center
      • Principal Investigator: Garth Nicholas, MD
    • Toronto, Ontario, Canada, M5G 0A3
      • Recruiting
      • Princess Margaret Cancer Centre
      • Principal Investigator: Geoffrey Liu, M.D.
• France
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
    • Principal Investigator: Aurelie Swalduz, MD
  • Nantes, France, 44093
    • Recruiting
    • CHU de NANTES
    • Principal Investigator: Elvire Pons-Tostivint, MD, PhD
  • Toulouse, France, 31059
    • Recruiting
    • Institut Claudius Regaud
    • Principal Investigator: Julien Mazieres, MD, PhD
  • Villejuif, France, 94805
    • Recruiting
    • Institute Gustave Roussy
    • Principal Investigator: Benjamin Besse, MD, PhD
• Germany
  • Cologne, Germany, 50937
    • Recruiting
    • Universitatsklinikum Koln - University Hospital Cologne
    • Principal Investigator: Dr med Sebastian Michels
  • Frankfurt, Germany, 60590
    • Recruiting
    • Universitätsklinikum Frankfurt
    • Principal Investigator: Martin Sebastian, MD
  • Großhansdorf, Germany, 22927
    • Recruiting
    • LungenClinic Großhansdorf GmbH
    • Principal Investigator: Prof Dr Martin Reck
  • Heidelberg, Germany, 69126
    • Recruiting
    • Universkitatsklinikum Heidelberg - University Hospital Heidelberg
    • Principal Investigator: Prof Dr med Petros Christopoulos
• Italy
  • Ancona, Italy, 60126
    • Recruiting
    • Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto
    • Principal Investigator: Rossana Berardi, MD
  • Bari, Italy, 70124
    • Recruiting
    • IRCCS Istituto Tumori "G. Paolo II"
    • Principal Investigator: Domenico Galetta, MD
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Principal Investigator: Sara Cresta, MD
  • Milan, Italy, 20141
    • Recruiting
    • Instituto Europeo di Oncologia
    • Principal Investigator: Gianluca Spitaleri, MD
  • Padova, Italy, 35128
    • Recruiting
    • Instituto Oncologico Veneto
    • Principal Investigator: Giulia Pasello, MD
  • Ravenna, Italy, 48100
    • Recruiting
    • Ospedale Santa Maria delle Croci
    • Principal Investigator: Chiara Bennati, MD
  • Rome, Italy, 00144
    • Recruiting
    • Regina Elena Institute for Cancer Research
    • Principal Investigator: Lorenza Landi, MD
• Japan
  • Kanagawa, Japan, 2418515
    • Recruiting
    • Kanagawa Cancer Center
    • Principal Investigator: Tetsuro Kondo, MD
  • Okayama, Japan, 7008558
    • Recruiting
    • Okayama University Hospital
    • Principal Investigator: Kiichiro Ninomiya, MD
  • Osaka, Japan, 5898511
    • Recruiting
    • Kindai University Hospital
    • Principal Investigator: Junko Tanizaki, MD
  • Shizuoka, Japan, 4118777
    • Recruiting
    • Shizuoka Cancer Center
    • Principal Investigator: Ryo Ko, MD PhD
  • Tokyo, Japan, 1040051
    • Recruiting
    • National Cancer Center Hospital
    • Principal Investigator: Tatsuya Yoshida, MD
  • Tokyo, Japan, 1358550
    • Recruiting
    • Cancer Institute Hospital of JFCR
    • Principal Investigator: Ryo Ariyasu, MD
  • Wakayama, Japan, 6418510
    • Recruiting
    • Wakayama Medical University Hospital
    • Principal Investigator: Hiroaki Akamatsu, MD, PhD
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Recruiting
    • The Netherlands Cancer Institute
    • Principal Investigator: Adrianus Joop de Langen, MD
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen (UMCG)
    • Principal Investigator: AJ Van Der Wekken, MD
• Singapore
  • Singapore
    • Singapore, Singapore, Singapore, 119074
      • Recruiting
      • National University Hospital
      • Principal Investigator: Ross Soo, MD
    • Singapore, Singapore, Singapore, 168583
      • Recruiting
      • National Cancer Centre Singapore
      • Principal Investigator: Aaron Tan, MD
• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
    • Principal Investigator: Dong-wan Kim, MD
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
    • Principal Investigator: Myung-Ju Ahn, MD
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital Yonsei University Health System
    • Principal Investigator: Byoung Chul Cho, MD
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • Recruiting
      • National Cancer Center
      • Principal Investigator: Ji-Youn Han, MD
• Spain
  • A Coruña, Spain, 15006
    • Recruiting
    • Complejo Hospitalario Universitario de A Coruña
    • Principal Investigator: Maria Campelo, MD
  • Barcelona, Spain, 08035
    • Recruiting
    • Vall d'Hebron
    • Principal Investigator: Enriqueta Felip, Md, PhD
  • Barcelona, Spain, 08017
    • Recruiting
    • UOMI Cancer Center
    • Principal Investigator: Santiago Viteri Ramirez, MD PhD
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Principal Investigator: Luis Paz Ares, MD, PhD
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital General Universitario Gregorio Marañón
    • Principal Investigator: Antonio Calles, MD
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Recruiting
    • Istituto Oncologico Svizzera Italiana
    • Principal Investigator: Patrizia Froesch, MD
  • Lucerne, Switzerland, 6000
    • Recruiting
    • Luzerner Kantonsspital
    • Principal Investigator: Anna Allemann, MD
• Taiwan
  • Taichung, Taiwan, 402306
    • Recruiting
    • Chung-Shan Medical University Hospital
    • Principal Investigator: Gee-Chen Chang, MD
  • Tainan, Taiwan, 70403
    • Recruiting
    • National Cheng Kung University Hospital
    • Principal Investigator: Chien-Chung Lin, MD
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
    • Principal Investigator: Josh Lin, MD
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Recruiting
    • Edinburgh Cancer Centre
    • Principal Investigator: Colin Barrie, MD
  • London, United Kingdom, SM2 5PT
    • Recruiting
    • The Royal Marsden - Chelsea
    • Principal Investigator: Anna Minchom MD
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
    • Principal Investigator: Matthew Krebs, MB ChB PhD
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Recruiting
      • Royal Marsden Hospital
      • Principal Investigator: Anna Minchom, MB BCh MRCP MD
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California Irvine Medical Center
      • Principal Investigator: Misako Nagasaka, MD
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California, Davis Comprehensive Cancer Center
      • Principal Investigator: Jonathan Riess, MD
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford Cancer Institute
      • Principal Investigator: Joel Neal, MD, PhD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center
      • Principal Investigator: Ross Camidge, MD, PhD
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University Medical Center
      • Principal Investigator: Joshua Reuss, MD
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami; Sylvester Cancer Center
      • Principal Investigator: Gilberto de Lima Lopes, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute, Emory University
      • Principal Investigator: Ticiana Leal, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Principal Investigator: Marina Garassino, MD
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • John Hopkins University
      • Principal Investigator: Vincent Lam, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Jessica Lin, MD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Alice Shaw, MD
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Cancer Institute
      • Principal Investigator: Bindu Potugari, MD
  • Missouri
    • St Louis, Missouri, United States, 63310
      • Recruiting
      • Washington University School of Medicine Siteman Cancer Center
      • Principal Investigator: Saiama Waqar, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Alexander Drilon, MD
    • New York, New York, United States, 10016
      • Recruiting
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
      • Principal Investigator: Elaine Shum, MD
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Thomas Stinchcombe, MD
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • OSU Brain & Spine Hospital
      • Principal Investigator: Logan Roof, MD, MSCR
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania, Abramson Cancer Center
      • Principal Investigator: Charu Aggarwal, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon
      • Principal Investigator: Melissa Johnson, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center
      • Principal Investigator: Christina Baik, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation.

3. Phase 2

   1. Phase 2 Cohorts except 2f: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
   2. 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.
4. DDI sub-study cohorts: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
5. 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
6. 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
7. Adequate organ function and bone marrow reserve

Exclusion criteria:

1. Patient's cancer has a known oncogenic driver alteration other than ALK.
2. Known allergy/hypersensitivity to excipients of NVL-655.
3. Major surgery within 4 weeks of the study entry
4. Ongoing or anticancer therapy
5. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655)
Experimental: 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.	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655)
Experimental: 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.	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655)
Experimental: 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.	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655)
Experimental: Cohort 2e; Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655)
Experimental: 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.	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655)
Experimental: Phase 1 dose escalation; Neladalkib (NVL-655) oral daily dosing	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655)
Experimental: Cohort G (DDI sub-study); Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655); Drug: Midazolam; Oral Solution of Midazolam; Drug: Repaglinide; Oral Tablet of Repaglinide
Experimental: Cohort H (DDI sub-study); Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI	Drug: Neladalkib (NVL-655); Oral Tablet of Neladalkib (NVL-655); Drug: Itraconazole; Oral Solution of Itraconazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) (Phase 2)	To determine ORR as assessed by BICR	2-3 years after first patient dosed.
Recommended Phase 2 Dose (RP2D) (Phase 1)	To determine the RP2D	Within 21 days of last patient dosed during escalation
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
Dose limiting toxicities (DLTs) (Phase 1)	Define the dose limiting toxicities (DLTs)	Within the first 21 days of the first neladalkib (NVL-655) dose
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	Pre-dose and up to 24 hours post-dose
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	Pre-dose and up to 24 hours post-dose
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)	Pre-dose and up to 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS) (Phase 2)	Determine OS	Approximately 3 years
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)	Approximately 3 years
Quality of life assessment	Measure the quality of life in patients with cancer and/or lung cancer.	2-3 years after first patient dosed
Maximum plasma concentration, (Cmax) of neladalkib (NVL-655)	To determine the 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)	To determine the 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)	To determine the 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)	To determine the 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)	To determine the 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
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)	Pre-dose and up to 24 hours post-dose
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)	Pre-dose and up to 24 hours post-dose
Oral clearance (CL/F) of neladalkib (NVL-655)	To determine the oral clearance (CL/F) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Volume of distribution (Vz/F) of neladalkib (NVL-655)	To determine the volume of distribution (Vz/F) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Half-life (t1/2) of neladalkib (NVL-655)	To determine the half-life (t1/2) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Objective response rate (ORR) (Phase 1)	Determine ORR as assessed by Investigator	2-3 years after first patient dosed
Duration of response (DOR)	Determine DOR of neladalkib (NVL-655) until radiographic disease progression or death	2-3 years after first patient dosed
Clinical benefit rate (CBR)	Determine CBR of neladalkib (NVL-655)	2-3 years after first patient dosed
Time to response	Determine time to response of neladalkib (NVL-655)	Approximately 3 years
Progression-free survival (PFS)	Determine PFS of neladalkib (NVL-655) until radiographic disease progression or death	2-3 years after first patient dosed
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	Up to 3 months after last dose
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	Up to 3 months after last dose

Collaborators and Investigators

• Sponsor: Nuvalent Inc.
• Investigators: Study Director: Viola Zhu, MD, PHD, Nuvalent Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Benzazepines; Benzodiazepines; Triazoles; Piperazines; Midazolam; Itraconazole; repaglinide
• Other Study ID Numbers: NVL-655-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No