A Phase 1a/1b Study of ELVN-002 for the Treatment of Patients With HER2 Mutant Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 198
- 试验地点
- 39
- 主要终点
- Incidence of dose limiting toxicities in Phase 1a monotherapy
研究概览
简要总结
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.
详细描述
There are 4 parts to the trial. Part 1 is a dose escalation with ELVN-002 monotherapy for people with advanced stage solid tumors that have a HER2 mutation, amplification or high HER2 over-expression. Part 2 is an ELVN-002 monotherapy dose exploration where additional people may be enrolled at dose levels that have cleared the dose escalation in Part 1 to further evaluate the safety, tolerability, pharmacokinetics and clinical activity. Part 3 is a dose expansion of ELVN-002 monotherapy which will enroll up to 40 patients people with advanced stage HER2 mutant non-small cell lung cancer. Patients in Part 3 will be randomized 1:1 to receive one of two dose levels.
Part 4 is a combination dose escalation where, based on the results of Part 1 and 2, a combination of ELVN-002 and either fam-trastuzumab deruxtecan-nxki (in HER2 mutant non-small cell lung cancer) or trastuzumab emtansine (in HER2 positive breast cancer) will be evaluated for safety and tolerability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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)
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: ELVN-002 (Drug)
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.
干预措施: ELVN-002 (Drug)
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.
干预措施: ELVN-002 (Drug)
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.
干预措施: ELVN-002 (Drug)
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.
干预措施: Fam-Trastuzumab Deruxtecan-Nxki (Drug)
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.
干预措施: ELVN-002 (Drug)
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.
干预措施: Trastuzumab emtansine (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities in Phase 1a monotherapy
时间窗: 21 days
Incidence of adverse events in Phase 1a monotherapy
时间窗: 24 months
incidence of laboratory abnormalities in Phase 1a monotherapy
时间窗: 24 months
incidence of ECG abnormalities in Phase 1a monotherapy
时间窗: 24 months
incidence of ECG abnormalities in Phase 1a combination with T-DXd
时间窗: 24 months
incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)
时间窗: 42 days
Incidence of adverse events in Phase 1a combination with T-DXd
时间窗: 24 months
incidence of laboratory abnormalities in Phase 1a combination with T-DXd
时间窗: 24 months
incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)
时间窗: 42 days
Incidence of adverse events in Phase 1a combination with T-DM1
时间窗: 24 months
incidence of laboratory abnormalities in Phase 1a combination with T-DM1
时间窗: 24 months
incidence of ECG abnormalities in Phase 1a combination with T-DM1
时间窗: 24 months
Incidence of adverse events in Phase 1b monotherapy
时间窗: 24 months
incidence of laboratory abnormalities in Phase 1b monotherapy
时间窗: 24 months
incidence of ECG abnormalities in Phase 1b monotherapy
时间窗: 24 months
次要结局
- Objective Response rate in Phase 1a monotherapy(24 months)
- Objective response rate in Phase 1b monotherapy(24 months)
- Duration of response in Phase 1b monotherapy(24 months)
- Brain metastases response in Phase 1b monotherapy(24 months)
- PK parameter of area under the curve of ELVN-002 in Phase 1a monotherapy(21 days)
- PK parameter of maximum concentration of ELVN-002 in Phase 1a monotherapy(21 days)
- PK parameter of terminal half life of ELVN-002 in Phase 1a monotherapy(21 days)
- PK parameter of area under the curve of ELVN-002 in Phase 1b monotherapy(21 days)
- PK parameter of maximum concentration of ELVN-002 in Phase 1b monotherapy(21 days)
- PK parameter of terminal half life of ELVN-002 in Phase 1b monotherapy(21 days)