A Phase 1 Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of CLN-418 in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 108
- 试验地点
- 7
- 主要终点
- Proportion of subjects with dose-limiting toxicity (DLT)
研究概览
简要总结
Study to evaluate the safety and tolerability of the study drug CLN-418, to determine the maximum tolerated dose and/or recommended Phase 2 study dose of CLN-418.
详细描述
This is a study to evaluate the safety and tolerability of the study drug CLN-418, and to determine the maximum tolerated dose and/or recommended Phase 2 study dose of CLN-418.
The study will also look at the anti-tumor activity, pharmacokinetics and immunogenicity of CLN-418.The study consists of 2 parts. In Part 1, patients are enrolled into different cohort doses in order to identify the appropriate recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD). In Part 2, participants with metastatic / unresectable Non small cell lung cancer (NSCLC), Triple Negative Breast Cancer (TNBC) will receive the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) established in Part 1 of the study. In Part 1 and Part 2, participants will be administered treatment every 3 weeks.
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
- •Willingness to sign a written informed consent document.
- •Male or female subject aged ≥18 years old at the time of screening.
- •Histologically or cytologically confirmed advanced solid tumors (e.g., breast cancer, ovarian cancer, endometrial cancer, cervical cancer, squamous cell non-small cell lung cancer (sNSCLC), cholangiocarcinoma, esophagus cancer, urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC)), followed by dose-expansion cohorts (Part 2) of subjects with advanced and/or metastatic non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC).or recurrent and progressed since last antitumor therapy for which no alternative, curative standard therapy exists.
- •Adequate organ and bone marrow function.
排除标准
- •Prior used anti-B7H4 and/or anti-4-1BB antibody treatment.
- •Immuno-oncology therapy or targeted anti-cancer therapy within 4 weeks prior to first dose of investigational product, any other anti-cancer therapy within 2 weeks prior to first dose of investigational product.
- •Not yet recovered from surgery or (immune-related) toxicity related with previous treatment.
- •Known history or active infection of hepatitis B or C.
- •History of cirrhosis or non-alcohol steatohepatitis, alcohol or drug-related, autoimmune hepatitis.
- •Known brain metastases or other central nervous system metastases that are either symptomatic or untreated that require concurrent treatment.
- •Active infection that requires treatment with antibiotics or antiviral treatment within 3 weeks prior to first dose of investigational product.
- •Known history of infection with human immunodeficiency virus or known acquired immunodeficiency syndrome (AIDS).
- •Known autoimmune disease.
- •Clinically significant cardiac condition.
- •Pregnant or breastfeeding women.
研究组 & 干预措施
CLN-418: Part 1
Experimental Part 1: Dose escalation
Intravenous IV administrations of CLN-418 on Day 1 of each 21 day treatment cycle
Dose for cohorts to be confirmed following consultation and approval by Safety Review Committee
干预措施: CLN-418 (Drug)
CLN-418: Part 2
Experimental Part 2: Dose Expansion
Treatment administered at Maximum Tolerated Dose (MTD) and / or Recommended Phase 2 Dose (RP2D) established in Part 1
干预措施: CLN-418 (Drug)
结局指标
主要结局
Proportion of subjects with dose-limiting toxicity (DLT)
时间窗: From Day 1 until day 21
Number of subjects who experienced DLT events during 21 days after first administration of CLN-418, divided by the number of DLT evaluable Subjects
次要结局
- Adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0(From signing of Informed Consent Form (ICF) till 84 days after last dose)
- Objective response rate, defined as the proportion of subjects with best overall response of complete response (CR) or partial response (PR) per RECIST 1.1(From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months)
- Disease control rate(From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months.)
- Maximal tumor shrinkage(From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months)
- Pharmacokinetics Analysis - Time Deviation(Up to 84 days post last dose)
- Duration of response(From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months)
- Duration of disease control(From time of consent until the first documented disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefits, death or study termination whichever comes first, assessed up to 12 months.)
- Pharmacokinetics Analysis - Serum Concentration(Up to 84 days post last dose)
- Anti-drug antibodies(Up to 84 days post last dose)