A Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics, and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 93
- 试验地点
- 9
- 主要终点
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of the study is to characterize the safety and pharmacokinetic (PK) profile of UCB6114 administered as monotherapy or in combination with selected standard of care (SOC) regimens.
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
- •Participant must be at least 18 years of age inclusive, at the time of signing the informed consent
- •Participant has advanced disease (ie, locally advanced or metastatic)
- •Participant has measurable or non-measurable disease as defined by the relevant Response Evaluation Criteria in Solid Tumors (RECIST)
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
- •Part A specific:
- •Participant has a histologically and/or cytologically confirmed diagnosis of one of the following advanced solid tumor types: colorectal adenocarcinoma, esophageal carcinoma, head and neck squamous cell carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, stomach adenocarcinoma, bladder urothelial carcinoma, or breast invasive carcinoma
- •Part B and C specific:
- •Participant has a histologically and/or cytologically confirmed diagnosis of one of the following advanced solid tumor types: colorectal adenocarcinoma, gastric adenocarcinoma, or adenocarcinoma of the gastroesophageal junction
- •Part A1 specific:
- •Participant has histologically and/or cytologically confirmed diagnosis of one of the following advanced solid tumor types: colorectal adenocarcinoma, gastric adenocarcinoma, adenocarcinoma of the gastroesophageal junction, or pancreatic cancer
排除标准
- •Participant has a known hypersensitivity to any components of the study medications or comparable drugs
- •Active and clinically significant bacterial, fungal, or viral infection, known infections with hepatitis B, hepatitis C, known human immunodeficiency virus, or acquired immunodeficiency syndrome related illness
- •Symptomatic central nervous system (CNS) malignancy or metastases. Screening of asymptomatic participants without history of CNS metastases is not required. Participants with asymptomatic CNS lesions should have completed standard therapy for their CNS lesions prior to study enrolment
- •Current hematologic malignancies
- •Prior organ or allogeneic stem-cell transplantation
- •QT interval corrected (QTc) >450 msec
- •Participant has impaired renal function
- •Alanine transaminase or AST are ≥2xULN (if liver metastases are present: ≥5xULN)
- •Participant has moderate or severe cardiovascular disease
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities other than liver metastases
研究组 & 干预措施
Part A
Study participants assigned this arm will receive UCB6114 as monotherapy in escalating cohorts at pre-specified dose levels.
干预措施: ginisortamab (Drug)
Part A1
Study participants will receive predefined doses of UCB6114 as monotherapy administered intravenously at pre-specified time points.
干预措施: ginisortamab (Drug)
Part B
Study participants assigned to this arm will receive UCB6114 in escalating cohorts at pre-specified dose levels in combination with trifluridine/tipiracil (TFD/TPI).
干预措施: ginisortamab (Drug)
Part B
Study participants assigned to this arm will receive UCB6114 in escalating cohorts at pre-specified dose levels in combination with trifluridine/tipiracil (TFD/TPI).
干预措施: trifluridine/tipiracil (Drug)
Part C
Study participants assigned to this arm will receive UCB6114 in escalating cohorts at pre-specified dose levels in combination with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) regimen.
干预措施: ginisortamab (Drug)
Part C
Study participants assigned to this arm will receive UCB6114 in escalating cohorts at pre-specified dose levels in combination with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) regimen.
干预措施: mFOLFOX6 (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From Baseline until the End of Study (up to 3.8 years)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication. A treatment-emergent adverse event (TEAE) was defined as any AE with a start date on or after the first dose of UCB6114 up until the last dose of Ginisortamab (UCB6114) +30 days (i.e. up to 3.8 years).
Percentage of Participants Based on Severity of Treatment-emergent Adverse Events
时间窗: From Baseline until the End of Study (up to 3.8 years)
AE is any untoward medical occurrence in patient or clinical study participant, temporally associated with use of study medication, whether or not considered related to study medication. AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of study medication. TEAE: any AE with start date on or after first dose of UCB6114 up until last dose of Ginisortamab(UCB6114)+30 days. Event for which no Common Terminology Criteria for AE (CTCAE) severity grade was recorded by investigator but intensity was recorded instead was assigned as follows to CTCAE severity grade:Severe=Grade 3, Life Threatening (indicated on electronic case report form (eCRF) for event that is serious)=Grade 4, Death (indicated on the eCRF for event that is serious or has outcome of death)=Grade 5. As planned, data reported for National Cancer Institute (NCI) CTCAE grade \>=3 TEAEs and related TEAEs.
Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: From Baseline throughout 28 days (Cycle 1)
DLT defined as any AE at least related to study medication that occurs during Cycle 1 and met following criteria: Grade (Gr) 3 or 4 nonhematological toxicity according to NCI CTCAE (Version 5.0) except for alopecia, or nausea, vomiting, or diarrhea that reverses to Gr ≤2 within 24 hours (hr) with appropriate medical therapy; Gr 3 or 4 biochemical abnormality that persists despite maximal supportive treatment or biochemical abnormalities that is symptomatic and nontransient; Any Gr ≥3 hematological toxicity of \>5 days duration or febrile neutropenia (absolute neutrophil count \[ANC\]\<1000/cubic millimeter\[mm3\] with single temperature of \>38.3°C or sustained temperature ≥38°C for more than one hr), infection with Gr 3 or 4 neutropenia, thrombocytopenia with bleeding or requiring platelet transfusion, or Gr 4 thrombocytopenia; Prolonged Gr 2 diarrhea (\>7 days) despite adequate antidiarrheal medication, or multiple Grade 1or 2 toxicities(eg, Gr 1 or 2 diarrhea, vomiting, rash, and fatigue).
次要结局
- Part A and A1: UCB6114 Serum Concentration by Scheduled Assessment and Cohort(Parts A: Cycle 1 (Day 1 end of infusion [EOI] and Day 15 Predose), Cycle 2 (Day 1 Predose and Day 15 Predose); Part A 1: Cycle 1 (Day 1 EOI and Day 15 Predose), Cycle 2 (Day 1 Predose))
- Part B and C: UCB6114 Concentration by Scheduled Assessment and Dose Level(Part B and C: Cycle 1 (Day 1 EOI and Day 15 Predose), Cycle 2 (Day 1 Predose and Day 15 Predose))