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 · tracked via the Priya Life Science Canada tracker

Sponsor

Nuvalent Inc

Phase

Phase 1/2

Started

2022-06-09

Last updated

2026-05-27

Condition(s) studied

Locally Advanced Solid TumorMetastatic Solid Tumor

Investigational drug(s) / intervention(s)

Neladalkib (NVL-655) →Midazolam →Repaglinide →Itraconazole →

Neladalkib (NVL-655): Oral Tablet of Neladalkib (NVL-655)

Midazolam: Oral Solution of Midazolam

Repaglinide: Oral Tablet of Repaglinide

Itraconazole: Oral Solution of Itraconazole

Study 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.

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

Eligibility

Sex

ALL

Min age

12 Years

Max age

—

Healthy volunteers

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.

Primary outcome measure(s)

Dose limiting toxicities (DLTs) (Phase 1) — Within the first 21 days of the first neladalkib (NVL-655) dose
Define the dose limiting toxicities (DLTs)
Recommended Phase 2 Dose (RP2D) (Phase 1) — Within 21 days of last patient dosed during escalation
To determine the RP2D
Objective Response Rate (ORR) (Phase 2) — 2-3 years after first patient dosed.
To determine ORR as assessed by BICR
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1) — Approximately 3 years
Incidence and severity of treatment-emergent adverse events (TEAEs)
Area under the curve of repaglinide (Phase 2 DDI sub-study) — Pre-dose and up to 24 hours post-dose
To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of repaglinide
Area under the curve of midazolam (Phase 2 DDI sub-study) — Pre-dose and up to 24 hours post-dose
To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of midazolam
Area under the curve of neladalkib (NVL-655) (Phase 2 DDI sub-study) — Pre-dose and up to 24 hours post-dose
To determine the effect of itraconazole on the single oral dose PK of neladalkib (NVL-655)

Trial sites (74)

Facility	City	Region	Status
University of California Irvine Medical Center	Orange	California	Recruiting
University of California, Davis Comprehensive Cancer Center	Sacramento	California	Recruiting
Stanford Cancer Institute	Stanford	California	Recruiting
University of Colorado Cancer Center	Aurora	Colorado	Recruiting
Georgetown University Medical Center	Washington D.C.	District of Columbia	Recruiting
University of Miami; Sylvester Cancer Center	Miami	Florida	Recruiting
Winship Cancer Institute, Emory University	Atlanta	Georgia	Recruiting
University of Chicago Medical Center	Chicago	Illinois	Recruiting
John Hopkins University	Baltimore	Maryland	Recruiting
Massachusetts General Hospital	Boston	Massachusetts	Recruiting
Dana Farber Cancer Institute	Boston	Massachusetts	Recruiting
Henry Ford Cancer Institute	Detroit	Michigan	Recruiting
Washington University School of Medicine Siteman Cancer Center	St Louis	Missouri	Recruiting
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York	Recruiting
Memorial Sloan Kettering Cancer Center	New York	New York	Recruiting
Duke University Medical Center	Durham	North Carolina	Recruiting
OSU Brain & Spine Hospital	Columbus	Ohio	Recruiting
University of Pennsylvania, Abramson Cancer Center	Philadelphia	Pennsylvania	Recruiting
Sarah Cannon	Nashville	Tennessee	Recruiting
MD Anderson Cancer Center	Houston	Texas	Active Not Recruiting
Fred Hutchinson Cancer Center	Seattle	Washington	Recruiting
Royal North Shore Hospital	Sydney	New South Wales	Recruiting
Princess Alexandra Hospital	Woolloongabba	Queensland	Recruiting
Peter MacCallum Cancer Centre	Melbourne	Victoria	Recruiting
Universitair Ziekenhuis Antwerpen (UZA)	Antwerp	Belgium	Recruiting
Universitaire Ziekenhuizen Leuven Campus Gastthuisberg	Leuven	Belgium	Recruiting
Cross Cancer Institute	Edmonton	Alberta	Recruiting
BC Cancer Center	Vancouver	British Columbia	Recruiting
The Ottawa Hospital Cancer Center	Ottawa	Ontario	Recruiting
Princess Margaret Cancer Centre	Toronto	Ontario	Recruiting
Centre Leon Berard	Lyon	France	Recruiting
Chu De Nantes	Nantes	France	Recruiting
Institut Claudius Regaud	Toulouse	France	Recruiting
Institute Gustave Roussy	Villejuif	France	Recruiting
Universitatsklinikum Koln - University Hospital Cologne	Cologne	Germany	Recruiting
Universitätsklinikum Frankfurt	Frankfurt	Germany	Recruiting
LungenClinic Grosshansdorf GmbH	Großhansdorf	Germany	Recruiting
Universkitatsklinikum Heidelberg - University Hospital Heidelberg	Heidelberg	Germany	Recruiting
Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto	Ancona	Italy	Recruiting
IRCCS Istituto Tumori "G. Paolo II"	Bari	Italy	Recruiting

+ 34 more sites — see the full list on the official registry below.

More Nuvalent Inc. trials in Canada

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

A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1) Recruiting

A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1) Recruiting

Other trials for the same condition

Study of Sacituzumab Govitecan in Participants With Metastatic Solid Tumors Active, not recruiting

A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1) Recruiting

A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or TransCon TLR7/8 Agonist or Other Anticancer Therapies in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies Active, not recruiting

First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors Recruiting

A Study Evaluating DS-1055a in Participants With Relapsed or Refractory Locally Advanced or Metastatic Solid Tumors Active, not recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05384626 on ClinicalTrials.gov ↗ ← All trials in Canada