Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05650879




Registration number
NCT05650879
Ethics application status
Date submitted
28/11/2022
Date registered
14/12/2022
Date last updated
7/06/2024

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
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05650879
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05650879