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

NCT06521554 | Recruiting Phase 1 FDA Drug

• 1 other identifier: NVL-330-01
• Study Type: interventional
• Target: 200
• Locations: 3 countries
• Sites: 21

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

Outcome Measures

Primary Outcomes (3)

• Recommended Phase 2 Dose (RP2D)

  To determine up to 2 RP2D Candidates

  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

  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

  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

  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

  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

  Pre-dose and up to 24 hours post-dose

• Effect of Food on Time of Maximum Concentration (Tmax) of NVL-330

  Pre-dose and up to 24 hours post-dose

• Maximum plasma concentration (Cmax) of NVL-330

  Pre-dose and up to 24 hours post-dose

Study Arms (2)

Phase 1a dose escalation

EXPERIMENTAL

NVL-330 oral daily dosing

Drug: NVL-330

Phase 1b dose expansion

EXPERIMENTAL

NVL-330 oral daily dosing

Drug: NVL-330

Interventions

NVL-330 DRUG

Oral Tablet of NVL-330

Phase 1a dose escalation; Phase 1b dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nuvalent Inc.: lead

Study Sites (21)

City of Hope - Lennar

Irvine, California, 92618, United States

RECRUITING

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Stanford Cancer Institute

Stanford, California, 94305, United States

RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Georgetown University Medical Center

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

RECRUITING

Sibley Memorial Hospital

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

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

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

Baltimore, Maryland, 21224, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Henry Ford Cancer Center

Detroit, Michigan, 48242, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

OSU Brain and Spine Hospital

Columbus, Ohio, 43210, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Chris O'Brien Lifehouse

Camperdown, New South Wales, NSW 2050, Australia

RECRUITING

North Shore Health Hub

Saint Leonards, New South Wales, 2065, Australia

RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

Princess Margaret Cancer Center - University Health Network

Toronto, Ontario, M5G 1L7, Canada

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Steve Margossian, MD PhD

  Nuvalent Inc.

  STUDY DIRECTOR

Central Study Contacts

Lisa Morelli

CONTACT

857-357-7000; clinicaltrials@nuvalent.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: July 26, 2024
• Study Start: July 18, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

AU (2); CA (2); US (17)