Locally Advanced Solid TumorPhase 1NCT06521554

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

A Phase 1 study testing NVL-330 in people with Locally Advanced Solid Tumor and Metastatic Solid Tumor, run by Nuvalent Inc. at 21 sites in 3 countries.

Recruiting

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

Sites and contacts

Official record

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Trial summary

Phase 1a/1b dose escalation and expansion study designed to evaluate the safety and tolerability of NVL-330, determine the recommended Phase 2 dose (RP2D), and evaluate the antitumor activity in participants with advanced or metastatic human epidermal growth factor receptor 2 (HER2) -altered non-small lung cancer… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Locally Advanced Solid Tumor, Metastatic Solid Tumor
What is being tested?: NVL-330
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 200 participants
Where: 21 sitesin 3 countries
Study dates: 18 Jul 2024to Feb 2027
Phase: Phase 1

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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age ≥ 18 years
Histologically or cytologically confirmed locally advanced or metastatic NSCLC
Documented HER2 status as follows:
Phase 1a: Documented oncogenic HER2 mutation such as HER2 exon20 insertion mutations or single nucleotide variants or HER2 amplification.
Phase 1b: Documented oncogenic HER2 mutation.
Identification of lesions as follows:

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Phase 1a: Must have evaluable disease (target or nontarget) according to RECIST 1.1.
Phase 1b: Must have measurable disease, defined as ≥ 1 radiologically measurable target lesion according to RECIST 1.1.
Adequate organ function and bone marrow reserve

Who cannot join

Participant's cancer has known oncogenic driver alteration other than HER2
Known allergy/hypersensitivity to excipients of NVL-330
Major surgery within 4 weeks of the first dose of study drug
Ongoing or recent anticancer therapy
Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study

Trial locations and contacts

21 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Lisa Morelli contact

857-357-7000

clinicaltrials@nuvalent.com

Country

City, postcode or hospital

Sites recruiting now only

21 sites in 3 countries

United States17 sites, 16 recruiting

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
Susan Scott, MD
Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Zofia Piotrowska, MD MHS
Recruiting
OSU Brain and Spine Hospital
Columbus, Ohio, 43210
Dwight Owen, MD
Recruiting
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
Gerald Falchook, MD MS
Recruiting
Henry Ford Cancer Center
Detroit, Michigan, 48242
Shirish Gadgeel, MD
Recruiting
NEXT Virginia
Fairfax, Virginia, 22031
Alexander Spira, MD PhD FACP
Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Haniel Araujo, MD
Recruiting
City of Hope - Lennar
Irvine, California, 92618
Danny Nguyen, MD
Recruiting
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Gilberto de Lima Lopes, Jr., MD
Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
Melissa Johnson, MD
Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Fernando Santini, MD
Recruiting
University of California, Davis Comprehensive Cancer Center
Sacramento, California, 95817
Jonathan Riess, MD
Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Rebecca Wood, 206-606-6970
Christina Baik, MD
Recruiting
Washington University
St Louis, Missouri, 63110
Completed
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
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Susan Scott, MD
Recruiting

Other trials in United States

Australia2 sites, 2 recruiting

Chris O'Brien Lifehouse
Camperdown, New South Wales, NSW 2050
Steven Kao, MD
Recruiting
North Shore Health Hub
Saint Leonards, New South Wales, 2065
Nick Pavlakis, MD
Recruiting

Other trials in Australia

Canada2 sites, 2 recruiting

Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Clinical Trial Unit
Recruiting
Princess Margaret Cancer Center - University Health Network
Toronto, Ontario, M5G 1L7
Geoffrey Liu, MD
Recruiting

Other trials in Canada

About this study

Official title: A Phase 1a/1b Study of the Selective Tyrosine Kinase Inhibitor NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1)

Phase 1a dose escalation is designed to assess the safety and tolerability of NVL-330 and to select the candidate RP2D(s) and, if applicable, the MTD.

Phase 1b expansion is designed to further evaluate the overall safety and tolerability of the candidate RP2D(s) of NVL-330 and to determine the RP2D of NVL-330 in participants with advanced or metastatic HER2 mutant NSCLC.

Read the detailed description

The planned Phase 1a/1b first-in-human study is designed as a two-part clinical trial to investigate NVL-330 in pre-treated participants with advanced or metastatic HER2-altered NSCLC. The dose escalation phase of the trial is designed to enroll a set number of participants per cohort at protocol defined dose levels.

After the initial participants are treated at a given dose level and monitored for at least 28 days, available data will be reviewed, and initiation of the next dosing group will proceed with consideration given to the overall safety profile.

The expansion phase of the trial is designed to further evaluate safety and activity and to confirm the RP2D(s).

Conditions: Locally Advanced Solid Tumor, Metastatic Solid Tumor
Being tested: NVL-330
Medical subject headings: Neoplasm Metastasis

What participants receive

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

NVL-330Drug
Oral Tablet of NVL-330

Study groups in NCT06521554
Study group	Role	What they receive
Phase 1a dose escalation	Experimental	NVL-330 oral daily dosing Receives: Drug: NVL-330
Phase 1b dose expansion	Experimental	NVL-330 oral daily dosing Receives: Drug: NVL-330

What is being measured

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

Recommended Phase 2 Dose (RP2D)
To determine up to 2 RP2D Candidates
Measured: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
Maximum Tolerated Dose (MTD)
If applicable, to determine the MTD
Measured: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
Incidence and severity of Treatment Emergent Adverse Events (TEAEs)
Number of participants with TEAEs as assessed by CTCAE, v5.0
Measured: First dose of study drug through 30 days after the last dose of study drug

Secondary outcomes (25)

Effect of Food on Maximum Plasma Concentration (Cmax) of NVL-330
To determine the effect of food on maximum plasma concentration (Cmax) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Effect of Food on Area Under the Curve from Time 0 to 24 (AUC0-24) of NVL-330
To determine the effect of food on area under the curve from time 0 to 24 of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Effect of Food on Area Under the Curve from Time 0 to Infinity (AUCinf) of NVL-330
To determine the effect of food on area under the curve from time 0 to infinity of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Effect of Food on Time of Maximum Concentration (Tmax) of NVL-330
To determine the effect of food on time of maximum concentration of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Maximum plasma concentration (Cmax) of NVL-330
To determine the maximum plasma concentration (Cmax) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Maximum plasma concentration (Cmax- dose normalized) of NVL-330
To determine the maximum plasma concentration (Cmax-dose normalized) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Plasma concentration at the end of the dosing interval (Ctau) of NVL-330
To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Plasma concentration 24 hours post-dose (C24) of NVL-330
To determine the plasma concentration 24 hours post-dose (C24) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Average plasma concentration (Cavg) of NVL-330
To determine the average plasma concentration (Cavg) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Time of maximum concentration (Tmax) of NVL-330
To determine the time of maximum concentration (Tmax) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Area Under the Curve at the End of the Dosing Interval (AUCtau) of NVL-330
To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Area Under the Curve at the End of the Dosing Interval (AUCtau - dose normalized) of NVL-330
To determine the area under the curve at the end of the dosing interval (AUCtau - dose normalized) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Area Under the Curve From Time 0 to 24 (AUC0-24) of NVL-330
To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Area Under the Curve From Time 0 to 24 (AUC0-24 - dose normalized) of NVL-330
To determine the area under the curve from time 0 to 24 (AUC0-24 - dose normalized) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Area Under the Curve From Time 0 to Infinity (AUCinf) of NVL-330
To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Area Under the Curve From Time 0 to Infinity (AUCinf - dose normalized) of NVL-330
To determine the area under the curve from time 0 to infinity (AUCinf - dose normalized) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Oral clearance (CL/F) of NVL-330
To determine the oral clearance (CL/F) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Volume of Distribution (Vz/F) of NVL-330
To determine the volume of distribution (Vz/F) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Accumulation Ratio of NVL-330
To determine the ratio of accumulation of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Half-life (t1/2) of NVL-330
To determine the half-life (t1/2) of NVL-330
Measured: Pre-dose and up to 24 hours post-dose
Objective Response Rate (ORR)
Objective Response Rate (ORR) as determined by RECIST 1.1 criteria
Measured: 2 -3 years after first participant dosed
Duration of Response (DOR)
Time from first investigator-assessed response to radiographic disease progression or death
Measured: 2 to 3 years after first participant dosed
Intracranial Objective Response Rate (IC-ORR)
The proportion of participants with a confirmed intracranial response (IC-CR or IC-PR)
Measured: 2 to 3 years after first participant dosed
Intracranial Duration of Response (IC-DOR)
The time from first investigator-assessed intracranial response to radiographic intracranial disease progression or death
Measured: 2 to 3 years after first participant dosed
Time to Response (TTR)
The time from first dose to first confirmed radiographic response
Measured: Approximately 3 years

Timeline

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

18 Jul 2024Feb 2027

First posted26 Jul 2024
Study start18 Jul 2024
Primary completionJan 2027 (estimated)
Study completionFeb 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Locally Advanced Solid TumorStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 200 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06521554
Sponsor's protocol ID: NVL-330-01
Status last verified: Oct 2026
First submitted: 22 Jul 2024
Last updated: 20 Oct 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Interested in taking part?

Lisa Morelli

857-357-7000

clinicaltrials@nuvalent.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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