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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06521554




Registration number
NCT06521554
Ethics application status
Date submitted
22/07/2024
Date registered
26/07/2024
Date last updated
11/05/2025

Titles & IDs
Public title
A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1)
Scientific 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)
Secondary ID [1] 0 0
NVL-330-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Solid Tumor 0 0
Metastatic Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NVL-330

Experimental: Phase 1a dose escalation - NVL-330 oral daily dosing

Experimental: Phase 1b dose expansion - NVL-330 oral daily dosing


Treatment: Drugs: NVL-330
Oral Tablet of NVL-330
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [1] 0 0
As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
Primary outcome [2] 0 0
Maximum Tolerated Dose (MTD)
Timepoint [2] 0 0
As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
Primary outcome [3] 0 0
Incidence and severity of Treatment Emergent Adverse Events (TEAEs)
Timepoint [3] 0 0
First dose of study drug through 30 days after the last dose of study drug
Secondary outcome [1] 0 0
Effect of Food on Maximum Plasma Concentration (Cmax) of NVL-330
Timepoint [1] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [2] 0 0
Effect of Food on Area Under the Curve from Time 0 to 24 (AUC0-24) of NVL-330
Timepoint [2] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [3] 0 0
Effect of Food on Area Under the Curve from Time 0 to Infinity (AUCinf) of NVL-330
Timepoint [3] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [4] 0 0
Effect of Food on Time of Maximum Concentration (Tmax) of NVL-330
Timepoint [4] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [5] 0 0
Maximum plasma concentration (Cmax) of NVL-330
Timepoint [5] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [6] 0 0
Maximum plasma concentration (Cmax- dose normalized) of NVL-330
Timepoint [6] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [7] 0 0
Plasma concentration at the end of the dosing interval (Ctau) of NVL-330
Timepoint [7] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [8] 0 0
Plasma concentration 24 hours post-dose (C24) of NVL-330
Timepoint [8] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [9] 0 0
Average plasma concentration (Cavg) of NVL-330
Timepoint [9] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [10] 0 0
Time of maximum concentration (Tmax) of NVL-330
Timepoint [10] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [11] 0 0
Area Under the Curve at the End of the Dosing Interval (AUCtau) of NVL-330
Timepoint [11] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [12] 0 0
Area Under the Curve at the End of the Dosing Interval (AUCtau - dose normalized) of NVL-330
Timepoint [12] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [13] 0 0
Area Under the Curve From Time 0 to 24 (AUC0-24) of NVL-330
Timepoint [13] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [14] 0 0
Area Under the Curve From Time 0 to 24 (AUC0-24 - dose normalized) of NVL-330
Timepoint [14] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [15] 0 0
Area Under the Curve From Time 0 to Infinity (AUCinf) of NVL-330
Timepoint [15] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [16] 0 0
Area Under the Curve From Time 0 to Infinity (AUCinf - dose normalized) of NVL-330
Timepoint [16] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [17] 0 0
Oral clearance (CL/F) of NVL-330
Timepoint [17] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [18] 0 0
Volume of Distribution (Vz/F) of NVL-330
Timepoint [18] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [19] 0 0
Accumulation Ratio of NVL-330
Timepoint [19] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [20] 0 0
Half-life (t1/2) of NVL-330
Timepoint [20] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [21] 0 0
Objective Response Rate (ORR)
Timepoint [21] 0 0
2 -3 years after first patient dosed
Secondary outcome [22] 0 0
Duration of Response (DOR)
Timepoint [22] 0 0
2 to 3 years after first patient dosed
Secondary outcome [23] 0 0
Intracranial Objective Response Rate (IC-ORR)
Timepoint [23] 0 0
2 to 3 years after first patient dosed
Secondary outcome [24] 0 0
Intracranial Duration of Response (IC-DOR)
Timepoint [24] 0 0
2 to 3 years after first patient dosed
Secondary outcome [25] 0 0
Time to Response (TTR)
Timepoint [25] 0 0
Approximately 3 years

Eligibility
Key inclusion criteria
1. Age = 18 years
2. Histologically or cytologically confirmed locally advanced or metastatic NSCLC
3. Documented HER2 status as follows:

1. Phase 1a: Documented oncogenic HER2 mutation such as HER2 exon20 insertion mutations or single nucleotide variants or HER2 amplification.
2. Phase 1b: Documented oncogenic HER2 mutation.
4. Identification of lesions as follows:

1. Phase 1a: Must have evaluable disease (target or nontarget) according to RECIST 1.1.
2. Phase 1b: Must have measurable disease, defined as = 1 radiologically measurable target lesion according to RECIST 1.1.
5. Adequate organ function and bone marrow reserve
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient's cancer has known oncogenic driver alteration other than HER2
2. Known allergy/hypersensitivity to excipients of NVL-330
3. Major surgery within 4 weeks of the first dose of study drug
4. Ongoing or recent anticancer therapy
5. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/07/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2026
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
North Shore Health Hub - Saint Leonards
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Nuvalent Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Steve Margossian, MD PhD
Address 0 0
Nuvalent Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Lisa Morelli
Address 0 0
Country 0 0
Phone 0 0
857-357-7000
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06521554