A First-in-human, Phase I, Open-label, Non-randomized, Multicentre Dose Escalation and Expansion Trial of BI 3810944 in Patients With Solid Tumours and Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 69
- 试验地点
- 7
- 主要终点
- Part A (dose escalation): Occurrence of Cytokine Release Syndrome (CRS) Grade 1 or 2 during the Maximum Tolerated Dose (MTD) evaluation period
研究概览
简要总结
This study is open to adults with advanced cancer (solid tumours) for whom previous treatment was not successful, or no treatment exists. The study tests different doses of BI 3810944 to find out which doses they can tolerate. Another purpose is to identify the most suitable dose of BI 3810944 and to find out whether it helps people with advanced cancer. BI 3810944 may help fight cancer.
Participants get BI 3810944 usually once every 3 weeks. At treatment start, it is given once a week for a short time. Participants may continue to get BI 3810944 as long as they benefit from treatment but no longer than 2 years. During this time, they regularly visit the study site. The first study visits include overnight stays at the hospital. At the visits, study doctors check participants' health, take necessary laboratory tests, and note any unwanted effects.
The doctors also regularly check the size of the tumour with imaging methods.
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
- •Trial participant population specifically to Part A and B:
- •Part A only: participants with any histologically or cytologically confirmed diagnosis of solid tumour who failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Participant must have exhausted available treatment options known to prolong survival for their disease.
- •Part B only: participants with histologically or cytologically confirmed diagnosis of who has progressed on, or is intolerant to available standard therapies, or for whom no standard therapy with proven benefit exists according to the local and institutional guidelines. Participants should not have received >3 previous lines of treatment (excluding prior systemic regimens received at adjuvant or neoadjuvant setting and excluding treatment with tumour-infiltrating lymphocytes at any timepoint). B-raf protein kinase (BRAF) mutation status must be known prior to screening
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- •Presence of at least one measurable lesion outside of central nervous system (CNS) as defined per response evaluation criteria in solid tumours (RECIST v 1.1)
- •Age ≥18 years
- •Adequate organ function
- •Life expectancy of ≥3 months at the start of the trial treatment in the opinion of the investigator
- •All toxicities related to previous anticancer therapies have resolved to common terminology criteria for adverse events (CTCAE) Grade ≤1 prior to trial treatment administration (except for alopecia and peripheral neuropathy which must be CTCAE Grade ≤2 and amenorrhea/menstrual disorders which can be any Grade) Further inclusion criteria apply.
排除标准
- •Active primary central nervous system (CNS) malignancy, active untreated CNS metastases and/or carcinomatous meningitis
- •Participants with asymptomatic (i.e. no clinical neurological symptoms) brain lesions are eligible provided they meet the following criteria:
- •Radiotherapy or surgery for brain metastases was completed ≥2 weeks before the first administration of BI 3810944
- •Patient is off steroids for ≥7 days (physiologic doses of steroids are permitted), and the patient is off anti-epileptic drugs for ≥7 days or on stable doses of anti-epileptic drugs for malignant CNS disease
- •A diagnosis of immunodeficiency; receiving chronic systemic therapy exceeding prednisone 10 mg daily or equivalent or any other form of immunosuppressive therapy within 7 days before the first dose of BI 3810944
- •Prior anticancer therapy:
- •Participants who have been treated with any other anticancer drug(s), within 28 days or within 5 half-life periods (whichever is shorter) prior to the first administration of BI 3810944
- •Participants who have been treated with extensive field radiotherapy including whole brain irradiation, within 2 weeks prior to first administration of BI 3810944
- •Prior treatment with organ transplant or hematopoietic stem-cell transplant
- •Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed (e.g. biopsy)
- •Women who are pregnant, breastfeeding or who plan to become pregnant or breastfeeding during the trial or within 4 months after the last dose of BI 3810944 Further exclusion criteria apply.
研究组 & 干预措施
Part A: Dose escalation
干预措施: BI 3810944 (Drug)
Part B: Dose expansion
干预措施: BI 3810944 (Drug)
结局指标
主要结局
Part A (dose escalation): Occurrence of Cytokine Release Syndrome (CRS) Grade 1 or 2 during the Maximum Tolerated Dose (MTD) evaluation period
时间窗: approximately 2 months
Part A (dose escalation): Occurrence of Dose Limiting Toxicity (DLTs) during the MTD evaluation period
时间窗: approximately 2 months
Part B (dose expansion): Objective Response (OR)
时间窗: up to 24 months
OR, defined as best overall response of confirmed CR and/or confirmed PR, where best overall response is determined according to RECIST v 1.1 assessed from first treatment administration until the earliest event of PD, death or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow up or withdrawal of consent
次要结局
- Parts A and B (dose escalation and dose expansion): Terminal half-life of BI 3810944 (t1/2)(up to 24 months)
- Part A (dose escalation): Occurrence of DLTs during the on-treatment period(approximately 2 months)
- Part A (dose escalation): Occurrence of Adverse Event (AEs) during the on-treatment period(approximately 2 months)
- Part B (dose expansion): Occurrence of AEs during the on-treatment period(up to 24 months)
- Part B (dose expansion): Duration of Response (DoR)(up to 24 months)
- Part B (dose expansion): Disease control (DC)(up to 24 months)
- Part B (dose expansion): Progression-free survival (PFS)(up to 24 months)
- Parts A and B (dose escalation and dose expansion): Maximum measured concentration of BI 3810944 in serum (Cmax)(up to 24 months)
- Parts A and B (dose escalation and dose expansion): Area under the serum concentration-time curve over the time interval from 0 to the last measured time point, tz (AUC0-tz)(up to 24 months)