An Open Label, Phase Ib, Dose-escalation Study Evaluating the Safety and Tolerability of Xentuzumab and Abemaciclib in Patients With Locally Advanced or Metastatic Solid Tumours and in Combination With Endocrine Therapy in Patients With Locally Advanced or Metastatic Hormone Receptor-positive, HER2-, Breast Cancer, Followed by Expansion Cohorts.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 133
- 试验地点
- 30
- 主要终点
- [Cohort A, B, C & D] Maximum Tolerated Dose (MTD) of Xentuzumab
研究概览
简要总结
This is a study in adult patients with different types of cancer. The purpose of this study is to find a safe dose of:
- Xentuzumab in combination with abemaciclib
- Xentuzumab in combination with abemaciclib and hormonal therapies The study also tests whether these medicines make tumours shrink in participants with lung and breast cancer.
Participants can stay in the study as long as they benefit from and can tolerate treatment. All participants get xentuzumab infusions and abemaciclib tablets. Participants who have breast cancer get different types of hormonal therapies in addition to xentuzumab and abemaciclib.
For all participants, the size of the tumour is measured regularly. Doctors also regularly check the general health of the participants."
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort A: Xentuzumab 1000 mg & 150 mg Abemaciclib
Patients with solid tumours received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal.
干预措施: Xentuzumab (Drug)
Cohort A: Xentuzumab 1000 mg & 150 mg Abemaciclib
Patients with solid tumours received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal.
干预措施: Abemaciclib (Drug)
Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 2.5 mg Letrozole (once daily film-coated tablet).
干预措施: Xentuzumab (Drug)
Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 2.5 mg Letrozole (once daily film-coated tablet).
干预措施: Abemaciclib (Drug)
Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 2.5 mg Letrozole (once daily film-coated tablet).
干预措施: Letrozole (Drug)
Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 1 mg Anastrozole (once daily film-coated tablet).
干预措施: Xentuzumab (Drug)
Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 1 mg Anastrozole (once daily film-coated tablet).
干预措施: Abemaciclib (Drug)
Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 1 mg Anastrozole (once daily film-coated tablet).
干预措施: Anastrozole (Drug)
Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Xentuzumab (Drug)
Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Abemaciclib (Drug)
Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Fulvestrant (Drug)
Cohort E: Xentuzumab 1000 mg & 150 mg Abemaciclib
Patients with non-small cell lung cancer (NSCLC) received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal.
干预措施: Xentuzumab (Drug)
Cohort E: Xentuzumab 1000 mg & 150 mg Abemaciclib
Patients with non-small cell lung cancer (NSCLC) received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal.
干预措施: Abemaciclib (Drug)
Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Xentuzumab (Drug)
Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Fulvestrant (Drug)
Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Abemaciclib (Drug)
Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & with visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Xentuzumab (Drug)
Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & with visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Fulvestrant (Drug)
Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & with visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Abemaciclib (Drug)
Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & with non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Xentuzumab (Drug)
Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & with non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Fulvestrant (Drug)
Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant
Patients with HR+ HER2- breast cancer & with non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
干预措施: Abemaciclib (Drug)
结局指标
主要结局
[Cohort A, B, C & D] Maximum Tolerated Dose (MTD) of Xentuzumab
时间窗: The first treatment cycle, up to 28 days.
MTD during the MTD evaluation period (the first 28 day cycle). The MTD is defined as the highest dose with \<25% risk of the true Dose limiting toxicity (DLT) rate \>33%. DLT: adverse event or laboratory abnormality which 1) is related, probably related or possibly related to study drug and 2) meets any of the following criteria, unless that toxicity can be attributed to cancer progression or to identified etiology: CTCAE grade (Gr). 3+ hyperglycaemia (\>48 hours), Gr. 4 hyperglycaemia, hematologic toxicity (\>5 days), Gr. 3+ pneumonitis, febrile neutropenia, thrombocytopenia (Gr. 4 any duration, Gr. 3 w/ bleeding), AST/ALT \> 5x ULN or \> (baseline + 4x ULN), Gr. 3+ diarrhoea, nausea, vomiting (\>2 days), skin rash, fatigue/asthenia (\>7 days), Gr. 3-4 hyperlipidaemia (\>2 weeks), Any AE causing 2-week treatment interruption, non-hematologic toxicities Gr. 3+ (except alopecia, infusion-related reaction), Any significant drug related toxicity qualified as DLT.
[Cohort A, B, C & D] Number of Patients With DLTs in the MTD Evaluation Period
时间窗: The first treatment cycle, up to 28 days.
Number of patients with Dose limiting toxicities in the MTD evaluation period. Dose limiting toxicity (DLT): adverse event or laboratory abnormality which 1) is related, probably related or possibly related to study drug and 2) meets any of the following criteria, unless that toxicity can be attributed to cancer progression or to identified etiology: CTCAE grade (Gr). 3+ hyperglycaemia (\>48 hours), Gr. 4 hyperglycaemia, hematologic toxicity (\>5 days), Gr. 3+ pneumonitis, febrile neutropenia, thrombocytopenia (Gr. 4 any duration, Gr. 3 w/ bleeding), AST/ALT \> 5x ULN or \> (baseline + 4x ULN), Gr. 3+ diarrhoea, nausea, vomiting (\>2 days), skin rash, fatigue/asthenia (\>7 days), Gr. 3-4 hyperlipidaemia (\>2 weeks), Any AE causing 2-week treatment interruption, non-hematologic toxicities Gr. 3+ (except alopecia, infusion-related reaction), Any significant drug related toxicity qualified as DLT.
[Cohort E] Number of Patients With Objective Response (OR)
时间窗: Up to 26.5 months
Objective response (OR) defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 from date of first treatment administration (including run-in for cohort E) until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeter (mm)). For non-target lesions: disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (\<10mm short axis). Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
[Cohorts D1 and D2] Progression Free Survival (PFS) at 18 Months
时间窗: Up to 18 months.
Progression free survival (PFS) rate at 18 month defined as the rate of absence of disease progression or death at the 18th month of treatment, where progression is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions: Unequivocal progression of existing non-target lesions (Note: the appearance of one or more new lesions is also considered progression). Reported is the progression free survival rate at 18 months, based on a Kaplan-Meier.
[Cohort F] Disease Control (DC)
时间窗: Up to 18.5 months.
Disease control (DC) defined as best overall response of complete response (CR) or partial response (PR) or confirmed stable disease (SD) (lasting for at least 24 weeks) or Non-CR/ Non-PD (lasting for at least 24 weeks) where best overall response is defined according to RECIST version 1.1 from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest sum diameters while on study.
次要结局
- [Cohorts E, D1 and D2] Disease Control (DC)(Up to 35.2 months.)
- [Cohorts E, F, D1 and D2] Time to Objective Response(Up to 21.9 months.)
- [Cohorts E, F, D1 and D2] Duration of Objective Response(Up to 27.2 months.)
- [Cohorts E, F, D1 and D2] Duration of Disease Control(Up to 33.1 months.)
- [Cohorts E, F, D1 and D2] Progression-free Survival (PFS)(Up to 33 months.)
- [Cohorts D1, D2 and F] Objective Response (OR)(Up to 35.2 months.)