ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer
- 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.
- Acronym
- Short title
- ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer
- Official title
- A Phase 1a/1b Study of ELVN-002 for the Treatment of Patients With HER2 Mutant Non-Small Cell Lung Cancer
- Control arm
- Open label
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Active, not recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2026-07-01
- First posted
- 2022-12-14
- Registry last updated
- 2025-07-15
- Primary completion date
- 2026-07-01
- Start date
- 2023-03-20
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Randomisation ratio
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Enliven Therapeutics
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05650879
- ClinicalTrials.gov ID
- NCT05650879
- Registry record
- Open registry record
- Allocation
- Not randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- No masking
Incidence of dose limiting toxicities in Phase 1a monotherapy
Timeframe: 21 days
Incidence of adverse events in Phase 1a monotherapy
Timeframe: 24 months
incidence of laboratory abnormalities in Phase 1a monotherapy
Timeframe: 24 months
incidence of ECG abnormalities in Phase 1a monotherapy
Timeframe: 24 months
incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)
Timeframe: 42 days
Incidence of adverse events in Phase 1a combination with T-DXd
Timeframe: 24 months
incidence of laboratory abnormalities in Phase 1a combination with T-DXd
Timeframe: 24 months
incidence of ECG abnormalities in Phase 1a combination with T-DXd
Timeframe: 24 months
incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)
Timeframe: 42 days
Incidence of adverse events in Phase 1a combination with T-DM1
Timeframe: 24 months
incidence of laboratory abnormalities in Phase 1a combination with T-DM1
Timeframe: 24 months
incidence of ECG abnormalities in Phase 1a combination with T-DM1
Timeframe: 24 months
Incidence of adverse events in Phase 1b monotherapy
Timeframe: 24 months
incidence of laboratory abnormalities in Phase 1b monotherapy
Timeframe: 24 months
incidence of ECG abnormalities in Phase 1b monotherapy
Timeframe: 24 months
Objective Response rate in Phase 1a monotherapy
Timeframe: 24 months
For patients with measurable disease at baseline, confirmed response per RECIST 1.1
Objective response rate in Phase 1b monotherapy
Timeframe: 24 months
Confirmed response per RECIST 1.1
Duration of response in Phase 1b monotherapy
Timeframe: 24 months
The time from the first response to progression or death per RECIST 1.1
Brain metastases response in Phase 1b monotherapy
Timeframe: 24 months
for patients with measurable brain metastases at baseline, the percent of patients who have a confirmed response per RECIST 1.1
PK parameter of area under the curve of ELVN-002 in Phase 1a monotherapy
Timeframe: 21 days
the concentration of ELVN-002 measured in the blood over 24 hours at steady state
PK parameter of maximum concentration of ELVN-002 in Phase 1a monotherapy
Timeframe: 21 days
the maximum concentration of ELVN-002 measured in the blood at any time point at steady state
PK parameter of terminal half life of ELVN-002 in Phase 1a monotherapy
Timeframe: 21 days
the half life of ELVN-002 calculated from the concentration of ELVN-002 in blood
PK parameter of area under the curve of ELVN-002 in Phase 1b monotherapy
Timeframe: 21 days
the concentration of ELVN-002 measured in the blood over 24 hours at steady state
PK parameter of maximum concentration of ELVN-002 in Phase 1b monotherapy
Timeframe: 21 days
the maximum concentration of ELVN-002 measured in the blood at any time point at steady state
PK parameter of terminal half life of ELVN-002 in Phase 1b monotherapy
Timeframe: 21 days
the half life of ELVN-002 calculated from the concentration of ELVN-002 in blood
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
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)
- University of Colorado - Anschutz Medical Campus - PPDSAurora, United States
- Advent Health OrlandoOrlando, United States
- BRCR Medical Center IncPlantation, United States
- Dana Farber Cancer InstituteBoston, United States
- NEXT/Virginia Cancer SpecialistsFairfax, United States
- Macquarie University HospitalWestmead, Australia
- Linear Clinical Research LimitedNedlands, Australia
- Blacktown HospitalDarlinghurst, Australia
- Hôpital de la Timone Centre d'essais en cancérologie de Marseille (CEPCM-CLIPP)Marseille, France
- Hôpital PontchaillouRennes, France
- Centre Francois BaclesseCaen, France
- EDOG - Institut Bergonie - PPDSBordeaux, France
- Centre Georges François LeclercDijon, France
- Centre Léon BerardLyon, France
- Institut Gustave Roussy (IGR)Villejuif, France
- Fondazione IRCCS San Gerardo dei TintoriMonza, Italy
- Fondazione del Piemonte per l'Oncologia (IRCCS)Candiolo, Italy
- SOC Oncologia Medica e dei Tumori lmmunocorrelati, Centro Di Riferimento Oncologico Di Aviano (CRO) IRCCSAviano, Italy
- Azienda Ospedaliero Universitaria delle MarcheAncona, Italy
- Fondazione Policlinico Universitario A. GemelliRoma, Italy
- Unità Operativa Oncologia medica ed EmatologiaRozzano, Italy
- The Catholic University of Korea, St. Vincent's HospitalSuwon, South Korea
- Gachon University Gil Medical CenterIncheon, South Korea
- Severence Hospital, Yonsei UniversitySeoul, South Korea
- Samsung Medical CenterSeoul, South Korea
And 14 more, listed on the interactive page.