Share

Save

ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer

PHASE1RECRUITING

The goal of this clinical trial is to test ELVN-002 in people with cancers that have an abnormal HER2 gene. The main question the trial aims to answer is if ELVN-002 is safe and tolerable at different doses. A second main question is to evaluate the concentration of ELVN-002 in the blood at different doses and to see how this correlates with safety and see how the concentration of drug changes over time.

The third main question is to see if ELVN-002 works to shrink cancers that have HER2 genetic abnormalities, particularly non-small cell lung cancer.

info
Simpliy with AI

Study details:

There are 4 parts to the trial. Part 1 is a dose escalation with ELVN-002 monotherapy for people with advanced stage solid tumors that have a HER2 mutation, amplification or high HER2 over-expression. Part 2 is an ELVN-002 monotherapy dose exploration where additional people may be enrolled at dose levels that have cleared the dose escalation in Part 1 to further evaluate the safety, tolerability, pharmacokinetics and clinical activity.

Part 3 is a dose expansion of ELVN-002 monotherapy which will enroll up to 40 patients people with advanced stage HER2 mutant non-small cell lung cancer. Patients in Part 3 will be randomized 1:1 to receive one of two dose levels. Part 4 is a combination dose escalation where, based on the results of Part 1 and 2, a combination of ELVN-002 and either fam-trastuzumab deruxtecan-nxki (in HER2 mutant non-small cell lung cancer) or trastuzumab emtansine (in HER2 positive breast cancer) will be evaluated for safety and tolerability.

info
Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Pathologically documented advanced stage solid tumor
  • Progressed following all standard treatment or not appropriate for standard treatment
  • HER2 mutation, HER2 amplification or HER2 positive based on local testing
  • Pathologically documented unresectable and/or metastatic non-squamous NSCLC
  • HER2 mutation identified by tissue (fresh or archival) or ctDNA. Local testing for up to 20 patients the remainder centrally confirmed.
  • Measurable disease
  • No known epidermal growth factor receptor (EGFR), ROS1, anaplastic lymphoma kinase (ALK), or BRAF V600E mutation
  • Progressed after receiving at least 1 prior systemic therapy including a platinum-based chemotherapy with or without immunotherapy, or not appropriate for standard treatment.
  • No prior HER2 tyrosine kinase inhibitor. Prior HER2 directed antibodies or anti-body drug conjugates are allowed
  • No limit on prior number of therapies
  • Pathologically documented advanced stage NSCLC
  • Progressed after receiving at least 1 prior systemic therapy.
  • HER2 mutation based on local/historical testing of tissue or circulating tumor DNA
  • No known EGFR, ROS1, ALK, or BRAF V600E mutation
  • No prior T-DXd
  • No clinically severe pulmonary compromise
  • No limit on prior number of therapies
  • Documented HER2 positive (Immunohistochemical [IHC] 3+ or IHC2+/in situ hybridization (ISH+) breast cancer
  • Must have previously received trastuzumab, a taxane, and T-DXd (if available and appropriate) in the metastatic setting.
  • No limit on prior number of therapies
  • No prior T-DM1
  • Eastern Cooperative Oncology Group performance status of 0-1
  • Left ventricular ejection fraction ≥ 50%
  • Platelet count ≥ 100 x 109/L
  • Hemoglobin ≥ 8.5 g/dL
  • Absolute neutrophil count ≥1.0 x 109/L
  • Total bilirubin < 1.5 times upper limit of normal range (ULN), except for patients with Gilbert's syndrome
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3 times ULN. In the setting of liver metastases < 5 times ULN.
  • Creatinine clearance ≥ 60 mL/minute

    • Exclusion criteria

  • Severe cardiac arrhythmias, requiring treatment, symptomatic congestive heart failure, myocardial infarction within 28 days prior to first dose, or unstable angina.
  • Another active malignancy within 2 years except basal cell skin cancer and carcinoma in situ treated curatively
  • Active or chronic liver disease
  • Active infection requiring systemic therapy within 14 days before the first dose
  • Brain lesion requiring immediate local therapy
  • Leptomeningeal disease
  • Uncontrolled seizures
  • Corrected QT interval (QTc) of >470 milliseconds (ms) females or >450 ms for males by Fridericia (QTcF)
    • info
    Simplify with AI

    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2023-03-20

    Primary completion: 2026-07-01

    Study completion finish: 2026-07-01

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

    trial

    Trial ID

    NCT05650879

    Intervention or treatment

    DRUG: ELVN-002

    DRUG: Fam-Trastuzumab Deruxtecan-Nxki

    DRUG: Trastuzumab emtansine

    Conditions

    • • HER2 Mutant Non-small Cell Lung Cancer
    • • HER2-positive Metastatic Breast Cancer
    • • HER2 Gene Mutation
    • • HER2 Amplification
    Image related to HER2 Mutant Non-small Cell Lung Cancer

    • Condition: HER2 Mutant Non-small Cell Lung Cancer, HER2-positive Metastatic Breast Cancer and more

    • DRUG: ELVN-002 and other drugs

    • Nedlands, Western Australia, Australia and more

    • Sponsor: Enliven Therapeutics

    You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

    Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

    Find a site

    Closest Location:

    Linear Clinical Research Limited

    Research sites nearby

    Select from list below to view details:

    • Linear Clinical Research Limited

      Nedlands, Western Australia, Australia

    • Macquarie University Hospital

      Westmead, New South Wales, Australia

    • Blacktown Hospital

      Darlinghurst, Not Specified, Australia

    Loading...

    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: Phase 1a Monotherapy Dose Escalation
    • ELVN-002 will be administered either once or twice daily. Each cohort of patients will receive a higher dose. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
    DRUG: ELVN-002
    • capsule
    EXPERIMENTAL: Phase 1a Monotherapy Dose Exploration
    • ELVN-002 will be administered either once or twice daily. A maximum of 80 patients will enroll in this arm. A maximum of 10 patients may be enrolled at a single dose or tumor type. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
    DRUG: ELVN-002
    • capsule
    EXPERIMENTAL: Phase 1b Monotherapy Dose Expansion
    • ELVN-002 will be administered either once or twice daily. A maximum of 40 patients will enroll in this arm. Patients will be randomized 1:1 to one of two dose levels.
    • ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
    DRUG: ELVN-002
    • capsule
    EXPERIMENTAL: Phase 1a Combination Dose Escalation with T-DXd
    • ELVN-002 will be administered either once or twice daily starting on Day 1. ELVN-002 is an oral capsule. Each cohort will receive a higher dose of ELVN-002. All patients in all cohorts will initiate with 5.4mg/kg of intravenous T-DXd once every 3 weeks starting on day 22 of the study. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
    DRUG: ELVN-002
    • capsule
    EXPERIMENTAL: Phase 1a Combination Dose Escalation with T-DM1
    • ELVN-002 will be administered either once or twice daily starting on Day 1. ELVN-002 is an oral capsule. Each cohort will receive a higher dose of ELVN-002. All patients in all cohorts will initiate with 3.6 mg/kg of intravenous T-DM1 once every 3 weeks starting on day 22 of the study. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
    DRUG: ELVN-002
    • capsule

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Incidence of dose limiting toxicities in Phase 1a monotherapyNot Specified21 days
    Incidence of adverse events in Phase 1a monotherapyNot Specified24 months
    incidence of laboratory abnormalities in Phase 1a monotherapyNot Specified24 months
    incidence of ECG abnormalities in Phase 1a monotherapyNot Specified24 months
    incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)Not Specified42 days
    Incidence of adverse events in Phase 1a combination with T-DXdNot Specified24 months
    incidence of laboratory abnormalities in Phase 1a combination with T-DXdNot Specified24 months
    incidence of ECG abnormalities in Phase 1a combination with T-DXdNot Specified24 months
    incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)Not Specified42 days
    Incidence of adverse events in Phase 1a combination with T-DM1Not Specified24 months
    incidence of laboratory abnormalities in Phase 1a combination with T-DM1Not Specified24 months
    incidence of ECG abnormalities in Phase 1a combination with T-DM1Not Specified24 months
    Incidence of adverse events in Phase 1b monotherapyNot Specified24 months
    incidence of laboratory abnormalities in Phase 1b monotherapyNot Specified24 months
    incidence of ECG abnormalities in Phase 1b monotherapyNot Specified24 months

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Objective Response rate in Phase 1a monotherapyFor patients with measurable disease at baseline, confirmed response per RECIST 1.124 months
    Objective response rate in Phase 1b monotherapyConfirmed response per RECIST 1.124 months
    Duration of response in Phase 1b monotherapyThe time from the first response to progression or death per RECIST 1.124 months
    Brain metastases response in Phase 1b monotherapyfor patients with measurable brain metastases at baseline, the percent of patients who have a confirmed response per RECIST 1.124 months
    PK parameter of area under the curve of ELVN-002 in Phase 1a monotherapythe concentration of ELVN-002 measured in the blood over 24 hours at steady state21 days
    PK parameter of maximum concentration of ELVN-002 in Phase 1a monotherapythe maximum concentration of ELVN-002 measured in the blood at any time point at steady state21 days
    PK parameter of terminal half life of ELVN-002 in Phase 1a monotherapythe half life of ELVN-002 calculated from the concentration of ELVN-002 in blood21 days
    PK parameter of area under the curve of ELVN-002 in Phase 1b monotherapythe concentration of ELVN-002 measured in the blood over 24 hours at steady state21 days
    PK parameter of maximum concentration of ELVN-002 in Phase 1b monotherapythe maximum concentration of ELVN-002 measured in the blood at any time point at steady state21 days
    PK parameter of terminal half life of ELVN-002 in Phase 1b monotherapythe half life of ELVN-002 calculated from the concentration of ELVN-002 in blood21 days

    Frequently Asked Questions

    Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

    No questions submitted. Be the first to ask a question!

    You may be eligible to participate in this trial based on your search.Apply for study
    Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

    References

    Clinical Trials Gov: ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer

    Other trails to consider

    Top searched conditions

    ABN: 29 640 485 105 © 2025 Clinrol