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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
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.
* 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
Phase 1a Combination Breast Cancer
* 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
All Phases
* 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 All Phases:
* 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)
Primary outcome measure(s)
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
Trial sites (39)
Facility
City
Region
Status
University of Colorado - Anschutz Medical Campus - PPDS
Aurora
Colorado
Advent Health Orlando
Orlando
Florida
BRCR Medical Center Inc
Plantation
Florida
Dana Farber Cancer Institute
Boston
Massachusetts
NEXT/Virginia Cancer Specialists
Fairfax
Virginia
Macquarie University Hospital
Westmead
New South Wales
Linear Clinical Research Limited
Nedlands
Western Australia
Blacktown Hospital
Darlinghurst
Australia
Hôpital de la Timone Centre d'essais en cancérologie de Marseille (CEPCM-CLIPP)
Marseille
Bouches-du-Rhône
Hôpital Pontchaillou
Rennes
Brittany Region
Centre Francois Baclesse
Caen
Calvados
EDOG - Institut Bergonie - PPDS
Bordeaux
Gironde
Centre Georges François Leclerc
Dijon
France
Centre Léon Berard
Lyon
France
Institut Gustave Roussy (IGR)
Villejuif
France
Fondazione IRCCS San Gerardo dei Tintori
Monza
Lombardy
Fondazione del Piemonte per l'Oncologia (IRCCS)
Candiolo
Piedmont
SOC Oncologia Medica e dei Tumori lmmunocorrelati, Centro Di Riferimento Oncologico Di Aviano (CRO) IRCCS
Aviano
Pordenone
Azienda Ospedaliero Universitaria delle Marche
Ancona
The Marches
Fondazione Policlinico Universitario A. Gemelli
Roma
Italy
Unità Operativa Oncologia medica ed Ematologia
Rozzano
Italy
The Catholic University of Korea, St. Vincent's Hospital
Suwon
Gyeonggido
Gachon University Gil Medical Center
Incheon
South Korea
Severence Hospital, Yonsei University
Seoul
South Korea
Samsung Medical Center
Seoul
South Korea
Seoul National University Hospital
Seoul
South Korea
Korea University Anam Hospital
Seoul
South Korea
Hospital Universitari Arnau de Vilanova
Lleida
Lleida
Hospital Universitario Virgen Macarena
Seville
Sevilla
START Barcelona Hospital HM Nou Delfos
Barcelona
Spain
Hospital Universitari Vall d'Hebrón
Barcelona
Spain
lnstitut Catala d'Oncologia (ICO) L'Hospitalet, Servicio de Oncologia Medica
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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