ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer

Launched by ENLIVEN THERAPEUTICS · Dec 6, 2022

Keywords

ClinConnect Summary

This clinical trial, called ELVN-002, is looking at a new treatment for patients with certain types of cancer that have a problem with the HER2 gene. Specifically, it’s focused on patients with HER2 mutant non-small cell lung cancer and HER2-positive metastatic breast cancer. The main goals of the study are to see if ELVN-002 is safe at different doses, how the drug behaves in the body over time, and if it can help shrink tumors in people with these HER2 genetic changes.

To be eligible for the trial, participants should have advanced cancer that hasn't responded to standard treatments or cannot be treated with them. They must have a confirmed HER2 mutation or amplification and be in generally good health, without severe heart problems or other significant medical issues. Participants can expect to receive close monitoring during the trial, including blood tests and scans to track their health and the effects of the treatment. This trial is currently recruiting individuals aged 65 and older, and it aims to provide important information about how effective and safe ELVN-002 may be for patients facing these challenging cancers.

Gender

ALL

Eligibility criteria

• 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)