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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05650879




Registration number
NCT05650879
Ethics application status
Date submitted
28/11/2022
Date registered
14/12/2022

Titles & IDs
Public title
ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer
Scientific title
A Phase 1a/1b Study of ELVN-002 for the Treatment of Patients with HER2 Mutant Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
ELVN-002-001
Universal Trial Number (UTN)
Trial acronym
HER2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2 Mutant Non-small Cell Lung Cancer 0 0
HER2-positive Metastatic Breast Cancer 0 0
HER2 Gene Mutation 0 0
HER2 Amplification 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ELVN-002
Treatment: Drugs - Fam-Trastuzumab Deruxtecan-Nxki
Treatment: Drugs - Trastuzumab emtansine

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.

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.

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.

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.

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.


Treatment: Drugs: ELVN-002
capsule

Treatment: Drugs: Fam-Trastuzumab Deruxtecan-Nxki
intravenous

Treatment: Drugs: Trastuzumab emtansine
intravenous
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities in Phase 1a monotherapy
Timepoint [1] 0 0
21 days
Primary outcome [2] 0 0
Incidence of adverse events in Phase 1a monotherapy
Timepoint [2] 0 0
24 months
Primary outcome [3] 0 0
incidence of laboratory abnormalities in Phase 1a monotherapy
Timepoint [3] 0 0
24 months
Primary outcome [4] 0 0
incidence of ECG abnormalities in Phase 1a monotherapy
Timepoint [4] 0 0
24 months
Primary outcome [5] 0 0
incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)
Timepoint [5] 0 0
42 days
Primary outcome [6] 0 0
Incidence of adverse events in Phase 1a combination with T-DXd
Timepoint [6] 0 0
24 months
Primary outcome [7] 0 0
incidence of laboratory abnormalities in Phase 1a combination with T-DXd
Timepoint [7] 0 0
24 months
Primary outcome [8] 0 0
incidence of ECG abnormalities in Phase 1a combination with T-DXd
Timepoint [8] 0 0
24 months
Primary outcome [9] 0 0
incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)
Timepoint [9] 0 0
42 days
Primary outcome [10] 0 0
Incidence of adverse events in Phase 1a combination with T-DM1
Timepoint [10] 0 0
24 months
Primary outcome [11] 0 0
incidence of laboratory abnormalities in Phase 1a combination with T-DM1
Timepoint [11] 0 0
24 months
Primary outcome [12] 0 0
incidence of ECG abnormalities in Phase 1a combination with T-DM1
Timepoint [12] 0 0
24 months
Primary outcome [13] 0 0
Incidence of adverse events in Phase 1b monotherapy
Timepoint [13] 0 0
24 months
Primary outcome [14] 0 0
incidence of laboratory abnormalities in Phase 1b monotherapy
Timepoint [14] 0 0
24 months
Primary outcome [15] 0 0
incidence of ECG abnormalities in Phase 1b monotherapy
Timepoint [15] 0 0
24 months
Secondary outcome [1] 0 0
Objective Response rate in Phase 1a monotherapy
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Objective response rate in Phase 1b monotherapy
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Duration of response in Phase 1b monotherapy
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Brain metastases response in Phase 1b monotherapy
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
PK parameter of area under the curve of ELVN-002 in Phase 1a monotherapy
Timepoint [5] 0 0
21 days
Secondary outcome [6] 0 0
PK parameter of maximum concentration of ELVN-002 in Phase 1a monotherapy
Timepoint [6] 0 0
21 days
Secondary outcome [7] 0 0
PK parameter of terminal half life of ELVN-002 in Phase 1a monotherapy
Timepoint [7] 0 0
21 days
Secondary outcome [8] 0 0
PK parameter of area under the curve of ELVN-002 in Phase 1b monotherapy
Timepoint [8] 0 0
21 days
Secondary outcome [9] 0 0
PK parameter of maximum concentration of ELVN-002 in Phase 1b monotherapy
Timepoint [9] 0 0
21 days
Secondary outcome [10] 0 0
PK parameter of terminal half life of ELVN-002 in Phase 1b monotherapy
Timepoint [10] 0 0
21 days

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
198
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Macquarie University Hospital - Westmead
Recruitment hospital [2] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment hospital [3] 0 0
Blacktown Hospital - Darlinghurst
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Virginia
Country [5] 0 0
France
State/province [5] 0 0
Bouches-du-Rhône
Country [6] 0 0
France
State/province [6] 0 0
Brittany
Country [7] 0 0
France
State/province [7] 0 0
Calvados
Country [8] 0 0
France
State/province [8] 0 0
Cedex 8
Country [9] 0 0
France
State/province [9] 0 0
Côte-d'Or
Country [10] 0 0
France
State/province [10] 0 0
Gironde
Country [11] 0 0
France
State/province [11] 0 0
Villejuif Cedex
Country [12] 0 0
Italy
State/province [12] 0 0
Lombardia
Country [13] 0 0
Italy
State/province [13] 0 0
Marche
Country [14] 0 0
Italy
State/province [14] 0 0
Piemonte
Country [15] 0 0
Italy
State/province [15] 0 0
Pordenone
Country [16] 0 0
Italy
State/province [16] 0 0
Roma
Country [17] 0 0
Italy
State/province [17] 0 0
Rozzano
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Gyeonggido
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Incheon
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
L'Hospitalet de Llobregat
Country [23] 0 0
Spain
State/province [23] 0 0
Lleida
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Sevilla
Country [26] 0 0
Spain
State/province [26] 0 0
Valencia
Country [27] 0 0
Taiwan
State/province [27] 0 0
Taichung City
Country [28] 0 0
Taiwan
State/province [28] 0 0
Tainan
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taipei City

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Enliven Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Helen L Collins, MD
Address 0 0
Country 0 0
Phone 0 0
707 799-3272
Fax 0 0
Email 0 0
helen.collins@enliventherapeutics.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05650879