A First-in-human Open Label Phase Ia/Ib, Multicenter/Multiregional, Dose Escalation Study of BI 765883 Administered Intravenously as Monotherapy and in Combination With Gemcitabine and Nab-paclitaxel in Unselected Patients With Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) or Patients With PDAC Who Have Relapsed After Post-surgery Adjuvant Therapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 26
- 主要终点
- Occurrence of dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period
研究概览
简要总结
This study is open to adults with advanced pancreatic cancer for whom previous treatment was not successful or no treatment exists.
The purpose of this study is to find the highest dose of BI 765883 that people with advanced pancreatic cancer can tolerate when taken alone or together with chemotherapy. Another purpose is to check whether BI 765883 helps people with advanced pancreatic cancer. In this study, BI 765883 is given to humans for the first time.
Participants receive either BI 765883 alone or BI 765883 in combination with chemotherapy. Participants can stay in the study as long as they benefit from treatment and can tolerate it. At study visits, doctors collect information on any health problems of the participants and check the severity of participants' 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
- •Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
- •Of legal adult age (according to local legislation) at screening
- •Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be willing and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.
- •Histologically or cytologically confirmed Pancreatic ductal adenocarcinoma (PDAC)
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Life expectancy ≥3 months in the opinion of the investigator
- •Archived tumor tissue from a tissue core biopsy (e.g. paraffin-embedded formalin-fixed tissue blocks), OR fresh tumor tissue available for retrospective biomarker analysis; in both cases, a minimum of at least two core needle biopsies (18 gauge or greater) is required. Only non-significant risk procedures per the investigator's judgment will be used to obtain any biopsies specified in this study in cases where a fresh tumor biopsy is required.
- •Patients with at least 1 target lesion that can be accurately measured per RECIST version 1.1 Further inclusion criteria apply.
排除标准
- •Previous exposure to trial drug (BI 765883)
- •Any prior gemcitabine and/or paclitaxel therapy (for combination therapy cohorts)
- •Known hypersensitivity to the study medications or their excipients (including gemcitabine and nab-paclitaxel)
- •Any contraindications to gemcitabine or nab-paclitaxel according to the current approved local labels (combination therapy)
- •Currently enrolled in another investigational device or drug trial, or less than 28 days since ending another investigational device or drug trial(s) or receiving other investigational treatment(s)
- •Any serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease, active ulcers (gastrointestinal tract, skin), inflammatory bowel disease or bowel infection, or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the Investigator, would make the patient inappropriate for entry into the trial.
- •Prior radiotherapy or systemic therapy within 14 days prior to treatment start
- •History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of ≥III or IV, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the Investigator Further exclusion criteria apply.
研究组 & 干预措施
BI 765883 0.4 mg/kg, monotherapy
Participants received BI 765883 at a dose of 0.4 mg/kg, administered intravenously over a 30-minute infusion on Day 1 of each 2-week cycle.
干预措施: BI 765883 (Drug)
BI 765883 1.3 mg/kg, monotherapy
Participants received BI 765883 at a dose of 1.3 mg/kg, administered intravenously over a 30-minute infusion on Day 1 of each 2-week cycle.
干预措施: BI 765883 (Drug)
BI 765883 0.4 mg/kg + chemotherapy
Participants received BI 765883 at 0.4 mg/kg intravenously every 2 weeks as a 30-minute infusion. In addition, gemcitabine (1000 mg/m²) and nab-paclitaxel (125 mg/m²) were administered intravenously as 30-minute infusions on Day 1 of each 2-week cycle.
干预措施: BI 765883 (Drug)
BI 765883 0.4 mg/kg + chemotherapy
Participants received BI 765883 at 0.4 mg/kg intravenously every 2 weeks as a 30-minute infusion. In addition, gemcitabine (1000 mg/m²) and nab-paclitaxel (125 mg/m²) were administered intravenously as 30-minute infusions on Day 1 of each 2-week cycle.
干预措施: Gemcitabine (Drug)
BI 765883 0.4 mg/kg + chemotherapy
Participants received BI 765883 at 0.4 mg/kg intravenously every 2 weeks as a 30-minute infusion. In addition, gemcitabine (1000 mg/m²) and nab-paclitaxel (125 mg/m²) were administered intravenously as 30-minute infusions on Day 1 of each 2-week cycle.
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Occurrence of dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period
时间窗: Up to 28 days (2 treatment cycles)
phase Ia
Confirmed objective response (OR)
时间窗: Up to 350 days (25 treatment cycles)
phase Ib
Occurrence of Dose-Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period for the Determination of the Maximum Tolerated Dose (MTD)
时间窗: The MTD evaluation period corresponds to the first two treatment cycles (28 days), with extension up to 35 days in cases of early discontinuation, based on the residual effect period.
All Dose-Limiting Toxicities (DLTs) were agreed upon by the Dose-Escalation Committee (DEC) after review of the data from each cohort. Only Dose-Limiting Toxicities (DLTs) occurring in the first 2 cycles were considered necessary for dose-escalation decisions made by the Dose-Escalation Committee (DEC). Dose-Limiting Toxicities (DLTs) observed during the Maximum Tolerated Dose (MTD) evaluation period were considered for Maximum Tolerated Dose (MTD) determination. The MTD evaluation period was defined as the first two treatment cycles; i.e. from Cycle 1 Day 1 (C1D1) up to and including the day before C3D1, or to the end of the REP in case of discontinuation before the start of C3.
次要结局
- Objective response (OR)(Up to 350 days (25 treatment cycles))
- Recommended dose for expansion (RDE) for BI 765883 in combination with gemcitabine and nab-paclitaxel(Up to 28 days (2 treatment cycles))
- Frequency and severity of AEs according to the Common Terminology Criteria for Adverse Events (CTCAE)(Up to 350 days (25 treatment cycles))
- Maximum measured concentration of the analyte in serum (Cmax)(Up to 350 days (25 treatment cycles))
- Area under the serum concentration time curve of the analyte (AUC0-t)(Up to 350 days (25 treatment cycles))
- Progression-free survival (PFS)(Up to 350 days (25 treatment cycles))
- Duration of response (DOR)(Up to 350 days (25 treatment cycles))
- Best Overall Response as Defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(From the first trial drug administration until 35 days (the Residual Effect Period) after the last trial drug administration, covering a total duration of up to 134 days.)
- Disease Control as Defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(From the first trial drug administration until 35 days (the Residual Effect Period) after the last trial drug administration, covering a total duration of up to 134 days.)
- Objective Response (OR) as Assessed by the Investigator Defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(From the first trial drug administration until 35 days (the Residual Effect Period) after the last trial drug administration, covering a total duration of up to 134 days.)
- Maximum Measured Concentration of BI 765883 in Serum (Cmax)(Pharmacokinetic samples were collected predose (336 hrs after infusion start, prior to the next dose), at the start of infusion (0 hrs), after the end of infusion (0.5 hrs), and at 5, 24, 48, and 168 hrs after infusion start in Cycle 1 and Cycle 4.)
- Area Under the Concentration-Time Curve of BI 765883 From Time 0 to 336 Hours (AUC₀-336)(Pharmacokinetic samples were collected predose (336 hrs after infusion start, prior to the next dose), at the start of infusion (0 hrs), after the end of infusion (0.5 hrs), and at 5, 24, 48, and 168 hrs after infusion start in Cycle 1 and Cycle 4.)