Recruiting
Phase 1

NVL-330

Sponsor:

Nuvalent Inc.

Code:

NCT06521554

Conditions

Locally Advanced Solid Tumor

Metastatic Solid Tumor

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

NVL-330

Study Details

Brief 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 (NSCLC).

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.

Conditions

Locally Advanced Solid Tumor

Metastatic Solid Tumor

Study ID

NCT06521554

Start date

Jul 18, 2024

Status verified date

Feb, 2026

Completion date

Feb, 2027

Anticipated

Primary completion date

Jan, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Exclusion Criteria:

1. Participant'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

Enrollment

200 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1a dose escalation

NVL-330 oral daily dosing

experimental: Phase 1b dose expansion

NVL-330 oral daily dosing

Interventions

NVL-330

Oral Tablet of NVL-330

Primary outcome measure

  • Recommended Phase 2 Dose (RP2D) [ Time Frame: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1) ]
  • Maximum Tolerated Dose (MTD) [ Time Frame: 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) [ Time Frame: First dose of study drug through 30 days after the last dose of study drug ]

Central Contacts and Locations

Central contacts

Lisa Morelli

857-357-7000clinicaltrials@nuvalent.com

Locations

City of Hope - Lennar

Recruiting

Irvine, California, United States, 92618

Principal Investigator:

Danny Nguyen, MD

University of California, Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Principal Investigator:

Jonathan Riess, MD

Stanford Cancer Institute

Recruiting

Stanford, California, United States, 94305

Principal Investigator:

Joel Neal, MD PhD

Sarah Cannon Research Institute at HealthONE

Recruiting

Denver, Colorado, United States, 80218

Principal Investigator:

Gerald Falchook, MD MS

Georgetown University Medical Center

Recruiting

Washington D.C., District of Columbia, United States, 20007

Principal Investigator:

Joshua Reuss, MD

Sibley Memorial Hospital

Recruiting

Washington D.C., District of Columbia, United States, 20016

Principal Investigator:

Susan Scott, MD

Sylvester Comprehensive Cancer Center

Recruiting

Miami, Florida, United States, 33136

Principal Investigator:

Gilberto de Lima Lopes, Jr., MD

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bayview Medical Center

Recruiting

Baltimore, Maryland, United States, 21224

Principal Investigator:

Susan Scott, MD

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator:

Zofia Piotrowska, MD MHS

Henry Ford Cancer Center

Recruiting

Detroit, Michigan, United States, 48242

Principal Investigator:

Shirish Gadgeel, MD

Washington University

Recruiting

St Louis, Missouri, United States, 63110

Principal Investigator:

Maria Baggstrom, MD

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Fernando Santini, MD

OSU Brain and Spine Hospital

Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator:

Dwight Owen, MD

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

Melissa Johnson, MD

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Principal Investigator:

Haniel Araujo, MD

NEXT Virginia

Recruiting

Fairfax, Virginia, United States, 22031

Principal Investigator:

Alexander Spira, MD PhD FACP

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Contacts

Rebecca Wood

206-606-6970

Principal Investigator:

Christina Baik, MD

Cross Cancer Institute

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Princess Margaret Cancer Center - University Health Network

Recruiting

Toronto, Ontario, Canada, M5G 1L7

Principal Investigator:

Geoffrey Liu, MD

More Information

Sponsor

Nuvalent Inc.

Last update posted

Feb 25, 2026

Last verified

Feb, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Nuvalent Inc. on 2026-02-25.