NCT06521554

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

Recruiting now Phase 1 Last updated 23 February 2026

What this trial tests

Phase 1 trial testing NVL-330 in Locally Advanced Solid Tumor in 200 participants. Currently enrolling.

Timeline

18 July 2024

Primary endpoint
1 January 2027

1 February 2027

Quick facts

Lead sponsor	Nuvalent Inc.
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	200
Start date	18 July 2024
Primary completion	1 January 2027
Estimated completion	1 February 2027
Sites	21 locations across United States, Australia, Canada

Drugs / interventions tested

• NVL-330 — full drug profile →

Conditions studied

• Locally Advanced Solid Tumor — all drugs for Locally Advanced Solid Tumor →
• Metastatic Solid Tumor — all drugs for Metastatic Solid Tumor →

Sponsor

Nuvalent Inc. — full company profile →

Who can join

18 and older, any sex, with Locally Advanced Solid Tumor or Metastatic Solid Tumor. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Recommended Phase 2 Dose (RP2D)
  Time frame: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
  To determine up to 2 RP2D Candidates
• Maximum Tolerated Dose (MTD)
  Time frame: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
  If applicable, to determine the MTD
• 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
  Number of participants with TEAEs as assessed by CTCAE, v5.0

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. HER2 alterations in non-small cell lung cancer (NSCLC): from biology and testing to advances in treatment modalities.
   Ismail A, Desai A, Boumber Y. · · 2025 · cited 6× · PMID 40620714 · DOI 10.3389/fonc.2025.1624124
2. HER2 in Non-Small Cell Lung Cancer (NSCLC): Evolution of the Therapeutic Landscape and Emerging Drugs-A Long Way to the Top.
   Trillo Aliaga P, Spitaleri G, Attili I, Corvaja C, et al · · 2025 · cited 5× · PMID 40572608 · DOI 10.3390/molecules30122645
3. Epidemiology and Real-World Outcomes in Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Mutant Non-small Cell Lung Cancer by Region: A Targeted Literature Review.
   Goto K, Hayashi H, Maruti SS, Zettl H, et al · · 2026 · PMID 42090048 · DOI 10.1007/s11523-026-01213-4