A Phase 1 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BL-M14D1 in Subjects With Locally Advanced or Metastatic Small Cell Lung Cancer and Other Neuroendocrine Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 26
- 主要终点
- Participants with abnormal ECG and ECHO/MUGA reading
研究概览
简要总结
The objective of this study is to evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BL-M14D1 in Subjects with locally Advanced or Metastatic Small Cell Lung Cancer and Other Neuroendocrine Neoplasms
详细描述
A Phase 1 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BL-M14D1 in Subjects With Locally Advanced or Metastatic Small Cell Lung Cancer and Other Neuroendocrine Neoplasms
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented locally advanced or metastatic SCLC, large cell neuroendocrine cancer of the lung (LCNEC), neuroendocrine prostate cancer (NEPC), poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) or other extrapulmonary neuroendocrine carcinomas (EP-NECs), Merkel cell carcinoma (MCC), or other poorly differentiated and/or high-grade neuroendocrine neoplasms with evidence of DLL3 expression who have failed at least 1 line of standard therapy in the advanced/metastatic setting or are unable to receive standard treatment
- •Notes: For SCLC, the participant must have failed at least 1 line of platinum therapy in the advanced/metastatic setting.
- •No prior topoisomerase inhibitor-based ADC therapy is permitted.
- •In the dose expansion part, Cohort 6 (DLL3-Positive NEN Subgroup): participants will be eligible based on documented positive DLL3 expression.
- •At least one measurable lesion based on RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1
- •Toxicity of previous antitumor therapy has returned to Grade ≤1 as defined by National Cancer Institute (NCI) CTCAE v5.0, except for alopecia and endocrinopathies controlled by replacement therapy
- •No serious cardiac dysfunction and left ventricular ejection fraction ≥50%
- •Adequate organ function
排除标准
- •Chemotherapy, biological therapy, immunotherapy, , targeted therapy (including small molecule inhibitor of tyrosine kinase), and other antitumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; radical radiotherapy, major surgery within 4 weeks prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil drugs such as tegafur, capecitabine, or palliative radiotherapy within 2 weeks prior to initial administration.
- •Participants who have received prior topoisomerase inhibitor-based ADC therapy
- •Participants with other prior or concurrent malignancies except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after adequate resection, or other malignancy treated with curative intent with a disease-free interval of at least 3 years
- •Participants with advanced/ clinically significant lung diseases, such as poorly controlled chronic obstructive pulmonary disease (COPD) and asthma, restrictive lung disease, pulmonary hypertension etc.
- •Participants with primary neoplasms in the central nervous system (CNS), active or untreated CNS metastases, spinal cord compression, or carcinomatous meningitis should be excluded. Active brain metastases are defined as untreated symptomatic brain metastases or untreated brain metastases requiring systemic corticosteroids and/or anticonvulsants to control CNS-related symptoms. Patients with brain metastases are eligible if they meet any of the following criteria:
- •untreated, asymptomatic brain metastases
- •previously treated brain metastases may participate provided they are clinically stable with local therapy (eg, surgery or radiotherapy, currently asymptomatic, no longer requiring corticosteroid treatment, and recovered from all local therapy-related adverse events, as determined by the investigator
- •Participated in another clinical trial within 4 weeks prior to first dose of study treatment
- •Participants who are pregnant or breastfeeding, or planning to become pregnant during the study
- •Other conditions that the Investigator or Sponsor believes are not suitable for participating in this clinical trial
研究组 & 干预措施
Experimental BL-M14D1 administered Day 1 per cycle
BL-M14D1 will be administered on Day 1 by intravenous (IV) infusion every 3 weeks
干预措施: BL-M14D1 (Drug)
结局指标
主要结局
Participants with abnormal ECG and ECHO/MUGA reading
时间窗: 1 Year
Patients with abnormal ECG parameters (including the change from-baseline ECG parameters: heart rate \[HR\]; PR; QTcF; and QRS intervals \[∆HR, ∆PR, ∆QTcF, and ∆QRS\]), and ECHO/MUGA findings
Participants with Dose-limiting toxicities
时间窗: 1 Year
A DLT is defined as any of the following events: Toxicity that results in a \>14-day delay in treatment * Hematologic toxicities: * Grade 4 neutrophil count decreased lasting \>7 days * Grade ≥3 febrile neutropenia of any duration * Grade ≥3 platelet count decreased with clinically significant hemorrhage * Nonhematologic toxicities: * Death not related to disease progression or extraneous cause * Hy's law cases * Grade ≥3 nonhematologic toxicities, except for: * Grade 3 nausea/vomiting or diarrhea for less than 72 hours with adequate antiemetic and other supportive care * Grade 3 fatigue for less than 1 week * Grade ≥3 electrolyte abnormality that lasts up to 72 hours, is not clinically complicated, and resolves spontaneously or responds to conventional medical interventions * Grade ≥3 amylase or lipase that is not associated with symptoms or clinical manifestations of pancreatitis
Participants with Serious Adverse Events (SAEs) and treatment-emergent adverse events (TEAEs)
时间窗: 1 Year
Measuring the number of patients with serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)
Participants with abnormal physical examination findings
时间窗: 1 Year
Measure the number of participants with abnormal physical examination findings.
Participants with ability to care for themselves, daily activity, and physical activity
时间窗: 1 Year
Measure the change in participants with Eastern Clinical Oncology Group (ECOG) Scale of Performance Status. The scale is 0-4 with 0 being the fully active (best outcome) and 4 being completely disabled (worst outcome)
Participants with abnormal lab results
时间窗: 1 Year
Measure the number of participants with abnormal clinical laboratory values
To determine the maximum tolerated dose (MTD) if reached or maximum administered dose (MAD) and two or more recommended doses for expansion (RDEs) of BL-M05D1 in metastatic or unresectable tumors
时间窗: 1 Year
The actual number of subjects enrolled and dose levels to be explored in this study will depend on the MTD and/or RDE based on DLTs reported during the DLT observation period.
次要结局
- Cmax of BL-M14D1(1 Year)
- Cmax of anti-DLL3 antibodies(1 Year)
- Cmax of free payload ED-04(1 Year)
- Tmax of BL-M14D1(1 Year)
- Tmax of anti-DLL3 antibodies(1 Year)
- Tmax of free payload ED-04(1 Year)
- AUC(0-8) of BL-M05D1(1 Year)
- AUC(0-8) of anti-DLL3 antibodies(1 Year)
- AUC(0-8) of free payload ED-04(1 Year)
- AUC(last) of BL-M14D1(1 Year)
- AUC(last) of anti-DLL3 antibodies(1 Year)
- AUC(last) of free payload ED-04(1 Year)
- Overall Response Rate (ORR)(1 Year)
- Disease Control Rate (DCR)(1 Year)
- Time To Response (TTR)(1 Year)
- Progression-Free Survival (PFS)(1 Year)
- Overall Survival (OS)(1 Year)
- Duration of response (DoR)(1 Year)