AN OPEN-LABEL, MULTICENTER PHASE I STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND PRELIMINARY ANTI-TUMOR ACTIVITY OF ALPS12 IN PATIENTS WITH EXTENSIVE STAGE SMALL CELL LUNG CANCER
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 122
- 试验地点
- 6
- 主要终点
- Dose Escalation part : Dose-limiting toxicities (DLTs) and PK profile of ALPS12[safety and tolerability]
研究概览
简要总结
This study is a phase I, open-label, multicenter trial designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of ALPS12 in patients with extensive-stage small cell lung cancer. The study consists of two parts: a dose-escalation part and an expansion part.
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
- •Aged >18 years at time of informed consent
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- •Histologically documented extensive stage small cell lung cancer
- •Disease recurrence documented after at least one prior systemic therapy.
- •Confirmed availability of representative archival tumor specimens or fresh tumor specimen.
- •Measurable disease per RECIST v.1.
- •Adequate hematologic and end organ function
排除标准
- •Pregnant or breastfeeding, or intending to become pregnant or breastfeeding during the study
- •History or complication of clinically significant autoimmune disease
- •a positive HIV antibody test at screening
- •Active hepatitis B or hepatitis C
- •Prior treatment with anti-CD137 antibody drugs, anti-CD3 antibody drugs, and/or DLL3-targeted therapies
- •Patients who have received any investigational or approved anticancer therapy, including hormone therapy and/or radiotherapy, within 21 days prior to the first administration of the investigational drug.
- •History of Grade 4 immune-related adverse events caused by prior anti-PD-L1/PD-1 antibody drugs or anti-CTLA-4 antibody drugs (excluding asymptomatic elevations in serum amylase/lipase)
- •Patients who discontinued immunotherapy due to Grade 3 immune-related adverse events caused by prior anti-PD-L1/PD-1 antibody drugs or anti-CTLA-4 antibody drugs (excluding asymptomatic elevations in serum amylase/lipase), and/or patients who experienced Grade 3 immune-related adverse events caused by immunotherapy within 6 months prior to the first administration of the investigational drug
- •Patients who received a live attenuated vaccine within 4 weeks prior to the first administration of the investigational drug
- •History or clinical evidence of primary central nervous system (CNS) malignancy, symptomatic CNS metastases, CNS metastases requiring any anti tumor treatment, or leptomeningeal disease
- •Current or past CNS diseases (e.g., stroke, epilepsy, CNS vasculitis, neurodegenerative diseases)
研究组 & 干预措施
Dose escalation part
Patients will receive ALPS12 as a single agent following pretreatment of obinutuzumab to determine the MTD by evaluating DLTs in patients with extensive stage small cell lung cancer.
干预措施: ALPS12 (Drug)
Dose escalation part
Patients will receive ALPS12 as a single agent following pretreatment of obinutuzumab to determine the MTD by evaluating DLTs in patients with extensive stage small cell lung cancer.
干预措施: obinutuzumab (Drug)
Expansion part
Patients will receive ALPS12 as a single agent following pretreatment of obinutuzumab to evaluate the antitumor effect.
干预措施: ALPS12 (Drug)
Expansion part
Patients will receive ALPS12 as a single agent following pretreatment of obinutuzumab to evaluate the antitumor effect.
干预措施: obinutuzumab (Drug)
结局指标
主要结局
Dose Escalation part : Dose-limiting toxicities (DLTs) and PK profile of ALPS12[safety and tolerability]
时间窗: From Cycle 1 Day 1 to the administration of ALPS12 on Cycle 2 Day 1 (Cycle 1 is 21 days)
Nature and frequency of DLTs, AEs, PK and PD profiles
All part : Adverse events of ALPS12[safety and tolerability]
时间窗: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months)
Incidence, nature, and severity of AEs graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, and CRS and Immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to the ASTCT Consensus Grading Criteria
Dose Escalation part : Immunogenicity of ALPS12
时间窗: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months)
Incidence of ADAs to ALPS12 and potential correlation with PK parameters and safety
Expansion part : Preliminary anti-tumor activity of ALPS12 when administered at selected dose(s) based on tumor assessment in patients with extensive stage SCLC
时间窗: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months)
Objective response, defined as a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, as determined by the Investigators
次要结局
- Disease control [preliminary efficacy](From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months))
- Duration of response (DoR)[preliminary efficacy](From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months))
- Progression-free survival (PFS)[preliminary efficacy](From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months))
- Immunogenicity of obinutuzumab(From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months))
- Maximum serum concentration (Cmax) and Area under the concentration time-curve (AUC) of ALPS12 with obinutuzumab[PK profile](From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months))
- Adverse events of obinutuzumab[safety and tolerability](From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months))
- Overall survival (OS)[preliminary efficacy](From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months))
- Objective response rate(ORR)[preliminary efficacy](From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months))