A Phase 1a/1b Study of ELVN-002 for the Treatment of Patients with HER2 Mutant Non-Small Cell Lung Cancer

Protocol # :
HER2 Mutant Non-small Cell Lung Cancer
HER2-positive Metastatic Breast Cancer
HER2 Gene Mutation
HER2 Amplification
Disease Sites
Principal Investigator
Rotow, Julia, Kathleen

Trial Description

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 Requirements

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)