A First-In-Human Phase I, Open-Label, Dose-Escalating Trial to Assess the Safety, Tolerability and Immunogenicity/Preliminary Antitumor Activity of ES2B-C001 With or Without [Adjuvant] in HER2-expressing Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- To determine the safety, tolerability, maximum tolerated dose (MTD) for ES2B-C001 alone or in combination with [adjuvant].
研究概览
简要总结
The trial is a first-in-human, phase I, open-label, dose-escalating trial to assess the safety and tolerability of ES2B-C001 combined with or without [adjuvant], in patients with human epidermal growth factor receptor 2 (HER2) expressing metastatic breast cancer.
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
- •Patients aged ≥18 years at screening visit.
- •Diagnosis of HER2-expressing locally advanced, unresectable, or metastatic BC, with HER2 IHC level 1+, 2+ (either FISH negative or positive), or IHC level 3+, after undergoing 2-3 lines of anticancer therapy.
- •Life expectancy of at least 3 months.
- •ECOG performance status 0-
- •Patients have adequate bone marrow, kidney, liver, heart, and lung function without clinically significant laboratory parameters as judged by the investigator.
- •12-lead ECG without clinically significant abnormalities and no LBBB, QRS duration >140ms, or evidence of prior infarction.
- •Recovered from side effects, adverse reactions, or adverse events due to prior therapy and/or surgery; any residual toxicities and toxicities related to current anticancer treatment must be ≤ Grade 2, except for alopecia, neuropathy or lymphoedema.
- •If female, non-pregnant, postmenopausal, or practicing reliable contraception.
- •If male, sterilized or using reliable contraception.
排除标准
- •Any planned intravenous chemotherapy regimens or check point inhibitors, or previous therapy with those agents during the past 1 month and the patients are neutropenic. Maintenance therapy with a stable dose of HER2-directed mAbs or treatment with antibody drug conjugates (ADCs) for metastatic BC is allowed at the discretion of the treating physician.
- •Symptomatic CNS metastatic disease requiring treatment with high dose steroids (i.e., above 10 mg of prednisone or equivalent) within 14 days prior to first administration of ES2B-C001 (with or without adjuvant).
- •Concurrent or recent (within 21 days or 5 half-lives) involvement in any other clinical trial with an investigational drug, device, or other experimental intervention.
- •Concomitant severe or uncontrolled underlying medical and/or mental disease unrelated to the tumor, which in the opinion of the investigator is likely to compromise patient safety and affect the trial's outcome.
- •Previous documented coronary artery disease or congestive heart failure (>NYHA II).
- •Echocardiography with LVEF <55%.
- •Uncontrolled hypertension.
- •Active, known, or suspected autoimmune disease, except thyroid conditions sufficiently controlled on thyroid hormone therapy, and controlled insulin dependent diabetes.
- •Necessity for long-term immunosuppression (≤ 4 mg dexamethasone may be used transiently).
- •Systemic infection requiring intravenous antibiotics within 14 days before dosing.
- •Chronic use of anti-viral agents, except for human immunodeficiency virus (HIV) or hepatitis B or C virus (HBV, HCV) treatments.
- •History of severe hypersensitivity reactions to any of the trial drug components.
- •Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial treatment. Note: Administration of inactivated or recombinant vaccines/killed vaccines are allowed.
- •Birthmarks, tattoos, wounds, or skin conditions on deltoid region/buttocks that may obscure the assessment of injection site reactions.
- •Female patients who are pregnant, or lactating.
- •Any infection (including SARS-CoV-2), that in the opinion of the investigator would, upon inclusion in the trial, lead to potentially harming patients' safety or integrity.
研究组 & 干预措施
Cohort C3: 450µg ES2B-C001 with or without [adjuvant]
干预措施: ISA 51 VD (Other)
Cohort C1: 50µg ES2B-C001 with [adjuvant]
干预措施: ISA 51 VD (Other)
Cohort C2: 150µg ES2B-C001 with [adjuvant]
干预措施: ISA 51 VD (Other)
Cohort C3: 450µg ES2B-C001 with or without [adjuvant]
干预措施: ES2B-C001 (Biological)
Cohort C1: 50µg ES2B-C001 with [adjuvant]
干预措施: ES2B-C001 (Biological)
Cohort C2: 150µg ES2B-C001 with [adjuvant]
干预措施: ES2B-C001 (Biological)
结局指标
主要结局
To determine the safety, tolerability, maximum tolerated dose (MTD) for ES2B-C001 alone or in combination with [adjuvant].
时间窗: From enrolment to the end of study at week 18
* Nature and frequency of dose-limiting toxicities (DLTs). * Incidence, nature and severity of AEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. * Incidence, nature and severity of injection site reactions according to FDA Guidance on Toxicity Grading Scales in Vaccine Trials (FDA, 2007).
To determine the safety, tolerability, maximum tolerated dose (MTD) for ES2B-C001 alone or in combination with [adjuvant].
时间窗: From enrolment to the end of study at week 18
* Nature and frequency of dose-limiting toxicities (DLTs). * Incidence, nature and severity of AEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. * Incidence, nature and severity of injection site reactions according to FDA Guidance on Toxicity Grading Scales in Vaccine Trials (FDA, 2007).
次要结局
- To investigate the immunogenicity of ES2B-C001 alone or in combination with [adjuvant].(From enrolment to the end of study at week 18)
- To investigate the immunogenicity of ES2B-C001 alone or in combination with [adjuvant].(From enrolment to the end of study at week 18)