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

RecruitingPhase 1

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

Who can join

Ages 18 and older · All sexes

Full eligibility criteria

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

About the study

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.

What is being tested

NVL-330 (drug)

Sponsor: Nuvalent Inc. · Participants: 200 · Started: Jul 18, 2024

Contact the study team

Lisa Morelli · Phone: 857-357-7000

Official record on ClinicalTrials.gov — NCT06521554

Locations in the U.S.

California	City of Hope - Lennar, Irvine University of California, Davis Comprehensive Cancer Center, Sacramento Stanford Cancer Institute, Stanford
Colorado	Sarah Cannon Research Institute at HealthONE, Denver
District of Columbia	Georgetown University Medical Center, Washington D.C. Sibley Memorial Hospital, Washington D.C.
Florida	Sylvester Comprehensive Cancer Center, Miami
Maryland	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bayview Medical Center, Baltimore
Massachusetts	Massachusetts General Hospital, Boston
Michigan	Henry Ford Cancer Center, Detroit
Missouri	Washington University, St Louis
New York	Memorial Sloan Kettering Cancer Center, New York
Ohio	OSU Brain and Spine Hospital, Columbus
Tennessee	SCRI Oncology Partners, Nashville
Texas	The University of Texas MD Anderson Cancer Center, Houston
Virginia	NEXT Virginia, Fairfax
Washington	Fred Hutchinson Cancer Center, Seattle

Conditions

Metastatic Cancer

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.