Clinical trial • Phase I/II • Oncology
ELVN-002-1 for HER2-positive solid tumours | Colorectal adenocarcinoma | Breast cancer
Phase I/II trial of ELVN-002-1 for HER2-positive solid tumours | Colorectal adenocarcinoma | Breast cancer. open-label, adaptive. 119 participants.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- HER2-positive solid tumours | Colorectal adenocarcinoma | Breast cancer
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule | Monoclonal antibody
Key dates
- Initial CTIS Submission Date
- 24-04-2024
- First CTIS Authorization Date
- 14-08-2024
Trial design
open-label, adaptive Phase I/II trial across 24 sites in Netherlands, Italy, Spain and others.
- Open Label
- Yes
- Adaptive
- True, includes dose-escalation design with predefined dose levels and Safety Review Committee oversight to determine recommended doses (RD), dose-escalation cohorts in Part 1 and Part 2, expansion cohorts in Part 3/4 with planned futility analyses (e.g., futility after 10–12 participants have ≥2 post-baseline assessments), and protocol-specified stopping/continuation rules; chemotherapy may be discontinued per response or institutional SOC.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 119
Eligibility
Recruits 119 Vulnerable population selected (isVulnerablePopulationSelected: true). Specific details of consent/assent handling are not provided in the available structured data; subject information and informed consent form (ICF) documents (including pregnancy/partner ICFs) are listed among trial documents for country-specific use..
- Vulnerable Population
- Vulnerable population selected (isVulnerablePopulationSelected: true). Specific details of consent/assent handling are not provided in the available structured data; subject information and informed consent form (ICF) documents (including pregnancy/partner ICFs) are listed among trial documents for country-specific use.
Inclusion criteria
- {"criterion_text":"- 1. Participants ≥ 18 years of age at the time of signing the informed consent.\n- 2. Pathologically or histologically documented solid tumor.\n- 3. Locally advanced or relapsed/refractory disease or unresectable metastatic disease.\n- 4. HER2 positive disease (see protocol for futher information)\n- 5. Prior Treatment based on Study Part and Histological Tumor Type (see protocol for futher information)\n- 6. For Part 3 and Part 4 only (Phase 1b arms): at least 1 measurable lesion based on RECIST v1.1 within 6 weeks prior to first dose of ELVN-002.\n- 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n- 8. Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) (multigated acquisition [MUGA] allowed if ECHO cannot be performed) within 28 days of the first dose of ELVN-002"}
Exclusion criteria
- {"criterion_text":"- 1. Severe cardiac arrhythmias, requiring treatment, symptomatic congestive heart failure (≥ New York Heart Association Functional Classification [NYHAC] II), troponin levels consistent with myocardial infarction within 28 days prior to first dose of ELVN-002, or unstable angina.\n- 10. Treatment with other anticancer therapy according to protocol.\n- 11. Any brain lesion requiring immediate local therapy.\n- 12. Ongoing use of corticosteroids for central nervous system (CNS) symptoms at a dose of > 2 mg daily of dexamethasone (or equivalent) unless have Sponsor approval.\n- 13. Leptomeningeal disease.\n- 14. Uncontrolled seizures.\n- 15. Ongoing adverse effects from prior treatment > CTCAE Grade 1 except for Grade 2 alopecia\n- 16. Corrected QT interval (QTc) of >470 milliseconds (ms) females or >450 ms for males based on average of screening triplicate 12-lead ECG by Fridericia (QTcF)\n- 17. Known hypersensitivity to any component of ELVN-002 including inactive ingredients.\n- 18. Primary immunodeficiency or known HIV infection. Except patients with undetectable viral load (undetectable viral load must be documented while receiving, for at least 30 days, an anti-retroviral therapy that is not prohibited per Appendix 12).\n- 19. Known hypersensitivity to trastuzumab.\n- 2. History of another active malignancy within 2 years prior to the first dose except for previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively.\n- 20. For the combination with eribulin: known hypersensitivity to eribulin or dehydrated alcohol.\n- 21. For the combination cohorts with capecitabine: known hypersensitivity to capecitabine or anhydrous lactose, croscarmellose sodium, hydroxypropyl methylcellulose, microcrystalline cellulose, magnesium stearate, talc, titanium dioxide, and synthetic yellow and red iron oxides; known DPD deficiency.\n- 22. For the combination cohorts with 5-FU: known hypersensitivity to 5-FU or known DPD deficiency.\n- 23. For the combination with paclitaxel: known hypersensitivity to Polyoxyl 35 castor oil, NF, dehydrated alcohol, or Citric Acid.\n- 24. For the combination cohorts with oxaliplatin: known hypersensitivity oxaliplatin, any of the excipients or other platinum compounds.\n- 3. Serious medical or psychiatric illness likely to interfere with participation in this clinical trial.\n- 4. Major surgery within 3 weeks of the first dose of ELVN-002.\n- 5. Active or chronic liver disease, including active hepatitis B or C infection.\n- 6. Active infection requiring systemic therapy within 14 days before the first dose of ELVN-002.\n- 7. History of interstitial lung disease or pulmonary fibrosis.\n- 8. Participants for any chemotherapy cohort: ongoing Grade 2 or higher neuropathy of any cause\n- 9. Inability to swallow pills or any significant gastrointestinal disease which would preclude adequate oral absorption of medications."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Phase 1a: ELVN-002 + Trastuzumab: • Incidence of dose limiting toxicities (DLTs)","definition_or_measurement_approach":"Incidence of DLTs as reported during the DLT evaluation window (study-defined dose-limiting toxicities)"}
- {"endpoint_text":"- Phase 1a: ELVN-002 + Trastuzumab: • Incidence of adverse events (AEs), laboratory abnormalities, and electrocardiogram (ECG) abnormalities","definition_or_measurement_approach":"Incidence of AEs, laboratory and ECG abnormalities collected and graded per protocol (e.g., CTCAE) during treatment"}
- {"endpoint_text":"- Phase 1a: ELVN-002 + Trastuzumab + Chemotherapy: • Incidence of dose limiting toxicities (DLTs)","definition_or_measurement_approach":"Incidence of DLTs as recorded in the DLT evaluation window for combination cohorts"}
- {"endpoint_text":"- Phase 1a: ELVN-002 + Trastuzumab + Chemotherapy: • Incidence of dose limiting toxicities (DLTs)","definition_or_measurement_approach":"Incidence of DLTs (duplicate entry in source); measured during DLT evaluation window"}
- {"endpoint_text":"- Phase 1a: ELVN-002 + Trastuzumab + Chemotherapy: • Incidence of adverse events (Aes), laboratory abnormalities, and electrocardiogram (ECG) abnormalities","definition_or_measurement_approach":"Incidence of AEs, laboratory and ECG abnormalities during treatment as recorded per protocol"}
Secondary endpoints
- {"endpoint_text":"- Phase 1a: ELVN-002 plasma concentrations and PK parameters, including: area under the curve (AUC), maximum concentration (Cmax), timeat which Cmax is observed (Tmax), minimum concentration (Cmin), terminal half-life (T1/2), and other parameters such as dose proportionality and accumulation ratio","definition_or_measurement_approach":"Plasma concentrations and PK parameters measured from blood samples; standard non-compartmental PK analyses (AUC, Cmax, Tmax, Cmin, T1/2, dose proportionality, accumulation ratio)"}
- {"endpoint_text":"- Phase 1a: Confirmed ORR as assessed by investigators per RECIST v1.1","definition_or_measurement_approach":"Objective response rate (ORR) confirmed by investigators per RECIST v1.1"}
- {"endpoint_text":"- Phase 1b: Confirmed ORR and DOR as assessed by ICR per RECIST v1.1","definition_or_measurement_approach":"Confirmed ORR and duration of response (DOR) assessed by independent central review per RECIST v1.1"}
- {"endpoint_text":"- Phase 1b: Brain metastases response","definition_or_measurement_approach":"Response of brain metastases assessed per protocol imaging criteria (as specified in protocol)"}
- {"endpoint_text":"- Phase 1b: ELVN-002 plasma concentrations","definition_or_measurement_approach":"Plasma concentration measurements of ELVN-002 in Phase 1b (PK sampling)"}
Recruitment
- Planned Sample Size
- 119
- Recruitment Window Months
- 31
- Consent Approach
- Adults (≥18 years) provide informed consent. Multiple country-specific ICF documents are listed (Dutch, Italian, Spanish, English, French and country-specific versions including BE language variants). Pregnancy/partner ICFs and pregnancy safety follow-up ICFs are listed among documents.
Geography
- Total Number Of Sites
- 24
- Total Number Of Participants
- 156
Netherlands
- Earliest CTIS Part Ii Submission Date
- 23-07-2024
- Latest Decision Or Authorization Date
- 11-08-2025
- Processing Time Days
- 384
- Number Of Sites
- 2
- Number Of Participants
- 12
Sites
- Site Name
- Stichting Radboud universitair medisch centrum
- Department Name
- Medical Oncology
- Contact Person Name
- Caroline Marie Louise Van Herpen
- Contact Person Email
- carla.vanherpen@radboudumc.nl
- Site Name
- Academisch Ziekenhuis Maastricht
- Department Name
- Medical Oncology
- Contact Person Name
- Loes Latten-Jansen
- Contact Person Email
- loes.jansen@mumc.nl
Italy
- Earliest CTIS Part Ii Submission Date
- 22-07-2024
- Latest Decision Or Authorization Date
- 11-08-2025
- Processing Time Days
- 385
- Number Of Sites
- 5
- Number Of Participants
- 36
Sites
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- UOC Fase 1
- Contact Person Name
- Gennaro Daniele
- Contact Person Email
- gennaro.daniele@policlinicogemelli.it
- Site Name
- Azienda Ospedaliero Universitaria Pisana
- Department Name
- Centro di Farmacologia Clinica per La Sperimentazione dei Farmaci
- Contact Person Name
- Chiara Cremolini
- Contact Person Email
- chiaracremolini@gmail.com
- Site Name
- Azienda USL IRCCS Di Reggio Emilia
- Department Name
- Unità Clinica di Fase 1 - Oncologia Medica Provinciale
- Contact Person Name
- Maria Banzi
- Contact Person Email
- maria.banzi@ausl.re.it
- Site Name
- Azienda Ospedaliero Universitaria Renato Dulbecco
- Department Name
- UOC Oncologia Medica Traslazionale- Centro Sperimentazioni di Fase I
- Contact Person Name
- Pierfrancesco Tassone
- Contact Person Email
- tassone@unicz.it
- Site Name
- Fondazione IRCCS San Gerardo Dei Tintori
- Department Name
- Centro Ricerca Fase 1
- Contact Person Name
- Marina Elena Cazzaniga
- Contact Person Email
- marinaelena.cazzaniga@irccs-sangerardo.it
Spain
- Earliest CTIS Part Ii Submission Date
- 27-06-2024
- Latest Decision Or Authorization Date
- 13-08-2025
- Processing Time Days
- 412
- Number Of Sites
- 10
- Number Of Participants
- 54
Sites
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Medical Oncology Department . Early Drug Development Unit (UITM)
- Contact Person Name
- Guzman Alonso Casal
- Contact Person Email
- galonso@vhio.net
- Site Name
- Hospital Universitari Dexeus Grupo Quironsalud
- Department Name
- Medical Oncology Service
- Contact Person Name
- Jose Manuel Pérez García
- Contact Person Email
- josemanuel.perez@quironsalud.es
- Site Name
- Hospital Beata Maria Ana
- Department Name
- Medical Oncology Department
- Contact Person Name
- Javier Cortés Castan
- Contact Person Email
- javier.cortes@maj3.health
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Medical Oncology
- Contact Person Name
- Guillermo Suay Montagud
- Contact Person Email
- guillermo_suay@iislafe.es
- Site Name
- Clinica Universidad De Navarra (Pamplona)
- Department Name
- Medical Oncology Service
- Contact Person Name
- Ignacio Matos Garcia
- Contact Person Email
- imatos@unav.es
- Site Name
- Fundacion Instituto Valenciano De Oncologia
- Department Name
- Medical Oncology
- Contact Person Name
- Marcos Melián Sosa
- Contact Person Email
- mmelian@fivo.org
- Site Name
- Hospital Hm Nou Delfos
- Department Name
- Medical Oncology Department
- Contact Person Name
- Tatiana Hernández Herrero
- Contact Person Email
- tatiana.hernandez@start-barcelona.com
- Site Name
- Clinica Universidad De Navarra (Madrid)
- Department Name
- Medical Oncology Service
- Contact Person Name
- Ignacio Matos Garcia
- Contact Person Email
- imatos@unav.es
- Site Name
- Hospital Quironsalud Barcelona
- Department Name
- Oncology Medical Service
- Contact Person Name
- Fabricio Racca
- Contact Person Email
- fracca@nextoncology.eu
- Site Name
- Hospital Universitario Fundacion Jimenez Diaz
- Department Name
- Medical Oncology Service
- Contact Person Name
- Bernard Doger de Speville Uribe
- Contact Person Email
- bernard.doger@startmadrid.com
Belgium
- Earliest CTIS Part Ii Submission Date
- 23-07-2024
- Latest Decision Or Authorization Date
- 11-08-2025
- Processing Time Days
- 384
- Number Of Sites
- 3
- Number Of Participants
- 18
Sites
- Site Name
- Centre hospitalier universitaire de Liege
- Department Name
- Centre Multidisciplinaire D'Oncologie Médicale
- Contact Person Name
- Pierre Freres
- Contact Person Email
- pfreres@chuliege.be
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Medical Oncology
- Contact Person Name
- Astrid De Cuyper
- Contact Person Email
- astrid.decuyper@saintluc.uclouvain.be
- Site Name
- GasthuisZusters Antwerpen
- Department Name
- Medical Oncology
- Contact Person Name
- Tom Van den Mooter
- Contact Person Email
- tom.vandenmooter@gza.be
France
- Earliest CTIS Part Ii Submission Date
- 23-07-2024
- Latest Decision Or Authorization Date
- 24-11-2025
- Processing Time Days
- 489
- Number Of Sites
- 4
- Number Of Participants
- 36
Sites
- Site Name
- Institut Regional Du Cancer De Montpellier
- Department Name
- Medical Oncology
- Contact Person Name
- Diego Tosi
- Contact Person Email
- diego.tosi@icm.unicancer.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Medical Oncology Pôle régional de cancérologie
- Contact Person Name
- Nicolas Isambert
- Contact Person Email
- nicolas.isambert@chu-poitiers.fr
- Site Name
- Institut de Cancérologie de l'Ouest
- Department Name
- Medical Oncology
- Contact Person Name
- Marie Robert
- Contact Person Email
- marie.robert@ico-unicancer.fr
- Site Name
- Institut De Cancerologie Strasbourg Europe
- Department Name
- Medical Oncology
- Contact Person Name
- Lauriane Eberst
- Contact Person Email
- l.eberst@icans.eu
Sponsor
Primary sponsor
- Full Name
- Enliven Therapeutics Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- PPD Global Limited
- Responsibilities
- Study Start Up and e-Filing; multiple study support responsibilities (see sponsor duties list)
- Name
- Syneos Health Inc.
- Responsibilities
- PK analysis
- Name
- Pharmaceutical Product Development LLC
- Responsibilities
- Lab Kits supply, Central Laboratory Repository
- Name
- Perceptive Informatics Inc.
- Responsibilities
- Electronic image transmission
Third parties
- {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"Biomarker (ctDNA/ tissue) Analysis","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"Clinical Supplies and Batch release","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Travel reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Electronic image transmission","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Clinical Supplies and Batch release","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"PPD Global Limited","duties_or_roles":"Study Start Up and e-Filing; additional responsibilities (codes:1,2,5,8,9,11,12,13,15)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Lab Kits supply, Central Laboratory Repository","organisation_type":"Pharmaceutical company"}
- {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"PK analysis","organisation_type":"Hospital/Clinic/Other health care facility"}
Investigational products
- Investigational Product Name
- ELVN-002
- Active Substance
- ELVN-002-1
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- 1
- Starting Dose
- 45 mg BID (Days 1-7; then 90 mg BID from Day 8 in initial cohort)
- Dose Levels
- 45 mg BID; 67.5 mg BID; 90 mg BID; 135 mg BID; 180 mg BID
- Frequency
- BID
- Maximum Dose
- 180 mg BID
- Dose Escalation Increase
- Initial 45 mg BID → 67.5 mg BID → 90 mg BID → 135 mg BID → 180 mg BID
- Investigational Product Name
- Trastuzumab (Herceptin)
- Active Substance
- Trastuzumab
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous (IV) infusion (protocol dosing); product record also lists subcutaneous use
- Route
- Intravenous
- Authorisation Status
- 2
- Starting Dose
- 8 mg/kg IV (C1 D2 loading dose)
- Frequency
- 8 mg/kg IV one dose (C1D2) then 6 mg/kg IV every 21 days (Cycles 2+)
- Combination Treatment
- Yes
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