A Phase 1a/1b Study of ELVN-002 Combined with Trastuzumab in Advanced Stage HER2+ Solid tumors, and ELVN-002 Combined with Trastuzumab and Chemotherapy in Advanced Stage HER2+ Colorectal Cancer and Breast Cancer
概览
- 阶段
- 1/2 期
- 状态
- 招募中
- 发起方
- Enliven Therapeutics Inc.
- 入组人数
- 156
- 试验地点
- 24
- 主要终点
- Phase 1a: ELVN-002 + Trastuzumab: • Incidence of dose limiting toxicities (DLTs)
概览
简要总结
Phase 1a: ELVN-002 + Trastuzumab: Evaluate the safety and tolerability of ELVN-002 in combination with trastuzumab in participants with advanced stage HER2 positive solid tumors. Determine the recommended dose(s) (RD) of ELVN-002 in combination with trastuzumab in participants with advanced stage HER2 positive solid tumors Phase 1a: ELVN-002 + Trastuzumab + Chemotherapy: Evaluate the safety and tolerability of treatment of ELVN-002 + trastuzumab + CAPEOX or mFOLFOX6 chemotherapy (capecitabine with oxaliplatin or 5-fluorouracil/leucovorin with oxaliplatin) in participants with advanced stage HER2 positive colorectal cancer. Evaluate the safety and tolerability of treatment of ELVN-002 + trastuzumab + chemotherapy (eribulin, capecitabine or paclitaxel), in participants with advanced stage HER2 positive breast cancer Determine the RD(s) of ELVN-002 when given in combination with trastuzumab and chemotherapy in participants with advanced stage HER2 positive colorectal cancer or breast cancer, or in combination with trastuzumab and paclitaxel in HER2 positive solid tumors Phase 1b: Evaluate the safety and tolerability of treatment with ELVN-002 and trastuzumab in HER2 positive colorectal and breast cancer, and in participants with advanced stage HER2 positive solid tumors. Evaluate the safety and tolerability of treatment with ELVN-002 + trastuzumab + chemotherapy (CAPEOX or mFOLFOX6) in participants with advanced stage HER2 positive colorectal cancer (CRC)
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Part 4: ELVN-002 Dose expansion + Trastuzumab +CAPEOX or mFOLFOX6 in HER2 positive CRC
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Participants ≥ 18 years of age at the time of signing the informed consent.
- •Pathologically or histologically documented solid tumor.
- •Locally advanced or relapsed/refractory disease or unresectable metastatic disease.
- •HER2 positive disease (see protocol for futher information)
- •Prior Treatment based on Study Part and Histological Tumor Type (see protocol for futher information)
- •For Part 3 and Part 4 only (Phase 1b arms): at least 1 measurable lesion based on RECIST v1.1 within 6 weeks prior to first dose of ELVN-
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) (multigated acquisition [MUGA] allowed if ECHO cannot be performed) within 28 days of the first dose of ELVN-002
排除标准
- •Severe cardiac arrhythmias, requiring treatment, symptomatic congestive heart failure (≥ New York Heart Association Functional Classification [NYHAC] II), troponin levels consistent with myocardial infarction within 28 days prior to first dose of ELVN-002, or unstable angina.
- •Treatment with other anticancer therapy according to protocol.
- •Any brain lesion requiring immediate local therapy.
- •Ongoing use of corticosteroids for central nervous system (CNS) symptoms at a dose of > 2 mg daily of dexamethasone (or equivalent) unless have Sponsor approval.
- •Leptomeningeal disease.
- •Uncontrolled seizures.
- •Ongoing adverse effects from prior treatment > CTCAE Grade 1 except for Grade 2 alopecia
- •Corrected QT interval (QTc) of >470 milliseconds (ms) females or >450 ms for males based on average of screening triplicate 12-lead ECG by Fridericia (QTcF)
- •Known hypersensitivity to any component of ELVN-002 including inactive ingredients.
- •Primary immunodeficiency or known HIV infection. Except patients with undetectable viral load (undetectable viral load must be documented while receiving, for at least 30 days, an anti-retroviral therapy that is not prohibited per Appendix 12).
结局指标
主要结局
Phase 1a: ELVN-002 + Trastuzumab: • Incidence of dose limiting toxicities (DLTs)
Phase 1a: ELVN-002 + Trastuzumab: • Incidence of dose limiting toxicities (DLTs)
Phase 1a: ELVN-002 + Trastuzumab: • Incidence of adverse events (AEs), laboratory abnormalities, and electrocardiogram (ECG) abnormalities
Phase 1a: ELVN-002 + Trastuzumab: • Incidence of adverse events (AEs), laboratory abnormalities, and electrocardiogram (ECG) abnormalities
Phase 1a: ELVN-002 + Trastuzumab + Chemotherapy: • Incidence of dose limiting toxicities (DLTs)
Phase 1a: ELVN-002 + Trastuzumab + Chemotherapy: • Incidence of dose limiting toxicities (DLTs)
Phase 1a: ELVN-002 + Trastuzumab + Chemotherapy: • Incidence of adverse events (Aes), laboratory abnormalities, and electrocardiogram (ECG) abnormalities
Phase 1a: ELVN-002 + Trastuzumab + Chemotherapy: • Incidence of adverse events (Aes), laboratory abnormalities, and electrocardiogram (ECG) abnormalities
次要结局
- Phase 1a: ELVN-002 plasma concentrations and PK parameters, including: area under the curve (AUC), maximum concentration (Cmax), timeat which Cmax is observed (Tmax), minimum concentration (Cmin), terminal half-life (T1/2), and other parameters such as dose proportionality and accumulation ratio
- Phase 1a: Confirmed ORR as assessed by investigators per RECIST v1.1
- Phase 1b: Confirmed ORR and DOR as assessed by ICR per RECIST v1.1
- Phase 1b: Brain metastases response
- Phase 1b: ELVN-002 plasma concentrations
研究者
Chief Medical Officer
Scientific
Enliven Therapeutics Inc.