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

NCT05650879 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ELVN-002-001
• Study Type: interventional
• Target: 198
• Locations: 7 countries
• Sites: 39

Brief Summary

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.

Conditions

HER2 Mutant Non-small Cell Lung Cancer; HER2-positive Metastatic Breast Cancer; HER2 Gene Mutation; HER2 Amplification

Keywords

HER2 genetic alterations; HER2 mutation; ELVN-002; Non-small cell lung cancer; HER-2 positive metastatic breast cancer; Enhertu; trastuzumab emtansine; fam-trastuzumab deruxtecan-nxki; Kadcyla

Outcome Measures

Primary Outcomes (15)

• Incidence of dose limiting toxicities in Phase 1a monotherapy

  21 days

• Incidence of adverse events in Phase 1a monotherapy

  24 months

• incidence of laboratory abnormalities in Phase 1a monotherapy

  24 months

• incidence of ECG abnormalities in Phase 1a monotherapy

  24 months

• incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)

  42 days

• Incidence of adverse events in Phase 1a combination with T-DXd

  24 months

• incidence of laboratory abnormalities in Phase 1a combination with T-DXd

  24 months

• incidence of ECG abnormalities in Phase 1a combination with T-DXd

  24 months

• incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)

  42 days

• Incidence of adverse events in Phase 1a combination with T-DM1

  24 months

• incidence of laboratory abnormalities in Phase 1a combination with T-DM1

  24 months

• incidence of ECG abnormalities in Phase 1a combination with T-DM1

  24 months

• Incidence of adverse events in Phase 1b monotherapy

  24 months

• incidence of laboratory abnormalities in Phase 1b monotherapy

  24 months

• incidence of ECG abnormalities in Phase 1b monotherapy

  24 months

Secondary Outcomes (10)

• Objective Response rate in Phase 1a monotherapy

  24 months

• Objective response rate in Phase 1b monotherapy

  24 months

• Duration of response in Phase 1b monotherapy

  24 months

• Brain metastases response in Phase 1b monotherapy

  24 months

• PK parameter of area under the curve of ELVN-002 in Phase 1a monotherapy

  21 days

Study Arms (5)

Phase 1a Monotherapy Dose Escalation

EXPERIMENTAL

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

Phase 1a Monotherapy Dose Exploration

EXPERIMENTAL

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

Phase 1b Monotherapy Dose Expansion

EXPERIMENTAL

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

Phase 1a Combination Dose Escalation with T-DXd

EXPERIMENTAL

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; Drug: Fam-Trastuzumab Deruxtecan-Nxki

Phase 1a Combination Dose Escalation with T-DM1

EXPERIMENTAL

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; Drug: Trastuzumab emtansine

Interventions

ELVN-002 DRUG

capsule

Phase 1a Combination Dose Escalation with T-DM1; Phase 1a Combination Dose Escalation with T-DXd; Phase 1a Monotherapy Dose Escalation; Phase 1a Monotherapy Dose Exploration; Phase 1b Monotherapy Dose Expansion

Fam-Trastuzumab Deruxtecan-Nxki DRUG

intravenous

Also known as: Enhertu, T-DXd

Phase 1a Combination Dose Escalation with T-DXd

Trastuzumab emtansine DRUG

intravenous

Also known as: Kadcyla, T-DM1

Phase 1a Combination Dose Escalation with T-DM1

Eligibility Criteria

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

You may qualify if:

• Phase 1a Monotherapy Dose Escalation and Exploration:
• 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
• Phase 1b Monotherapy
• 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
• Phase 1a Combination with T-DXd
• Pathologically documented advanced stage NSCLC
• Progressed after receiving at least 1 prior systemic therapy.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Enliven Therapeutics: lead

Study Sites (39)

University of Colorado - Anschutz Medical Campus - PPDS

Aurora, Colorado, 80045, United States

Location

Advent Health Orlando

Orlando, Florida, 32804, United States

Location

BRCR Medical Center Inc

Plantation, Florida, 33322, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

NEXT/Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Macquarie University Hospital

Westmead, New South Wales, 2145, Australia

Location

Linear Clinical Research Limited

Nedlands, Western Australia, 6009, Australia

Location

Blacktown Hospital

Darlinghurst, 2010, Australia

Location

Hôpital de la Timone Centre d'essais en cancérologie de Marseille (CEPCM-CLIPP)

Marseille, Bouches-du-Rhône, 13005, France

Location

Hôpital Pontchaillou

Rennes, Brittany Region, 35033, France

Location

Centre Francois Baclesse

Caen, Calvados, 14076, France

Location

EDOG - Institut Bergonie - PPDS

Bordeaux, Gironde, 33000, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Léon Berard

Lyon, 69373, France

Location

Institut Gustave Roussy (IGR)

Villejuif, 94805, France

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardy, 20900, Italy

Location

Fondazione del Piemonte per l'Oncologia (IRCCS)

Candiolo, Piedmont, 10060, Italy

Location

SOC Oncologia Medica e dei Tumori lmmunocorrelati, Centro Di Riferimento Oncologico Di Aviano (CRO) IRCCS

Aviano, Pordenone, 33081, Italy

Location

Azienda Ospedaliero Universitaria delle Marche

Ancona, The Marches, 60126, Italy

Location

Fondazione Policlinico Universitario A. Gemelli

Roma, 00168, Italy

Location

Unità Operativa Oncologia medica ed Ematologia

Rozzano, 20089, Italy

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggido, 16247, South Korea

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Severence Hospital, Yonsei University

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Korea University Anam Hospital

Seoul, South Korea

Location

Hospital Universitari Arnau de Vilanova

Lleida, Lleida, 25198, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, 41009, Spain

Location

START Barcelona Hospital HM Nou Delfos

Barcelona, 08023, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

lnstitut Catala d'Oncologia (ICO) L'Hospitalet, Servicio de Oncologia Medica

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Chen Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

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

Model Details: Phase 1 will be a dose escalation monotherapy according to the Bayesian Optimal Interval Design model Phase 1b will be a dose expansion: up to 40 patients randomized between 2 dose levels

Study Record Dates

• First Submitted: November 28, 2022
• First Posted: December 14, 2022
• Study Start: March 20, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); AU (3); TW (3); KR (6); FR (7); IT (6); ES (9)