A Phase 1b Study of Talimogene Laherparepvec in Combination With Atezolizumab in Subjects With Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 36
- 试验地点
- 17
- 主要终点
- Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
研究概览
简要总结
Approximately 36 DLT-evaluable subjects will be enrolled in this study. The locations of the study will be in the United States, Australia, Europe and Switzerland.
The goal of this study is to evaluate the safety of intrahepatic injection (directly into the liver) of talimogene laherparepvec in combination with intravenously administered atezolizumab in subjects with triple negative breast cancer and colorectal cancer with liver metastases.
详细描述
The Screening period is 28 days prior to study enrollment. This study has 2 Cohorts. Cohort 1: Triple Negative Breast Cancer and Cohort 2: Colorectal Cancer. These cohorts will enroll in parallel. There will be a Safety Follow-up period and a Long Term Follow-up period.
Drug Administration: The participants will receive the study drugs in cycles. If the participants are found to be eligible to take part in this study, they will receive talimogene laherparepvec as an injection into the hepatic (liver) metastatic sites on Day 1 of each cycle along with receiving atezolizumab by intravenous infusion on Day 1 of each cycle. Each cycle is 21 days for 6 cycles. There is an option for an additional 6 cycles after the first 6 intra-hepatic cycles. After the first radiographic assessment at week 10, if all injectable liver lesions have been injected but the 4.0 mL maximum volume has not been used, injection of clinically assessed non-hepatic cutaneous, subcutaneous, and nodal tumor lesions with or without ultrasound guidance will be permitted. Liver lesions should be prioritized over cutaneous, subcutaneous and nodal lesions.
Treatment will continue until a participant experiences a DLT (Dose Limiting Toxicity) evaluated in the DLT period (which is 2 cycles from initial dose), has CR (Complete Response), has need for an alternative anticancer therapy or experiences a safety concern.
Study Visits: Cycle 1 to Cycle 12 - The participant will have a physical exam along with vital signs and ECOG (Eastern Cooperative Oncology Group) performance level assessment. Blood (about 2 Tablespoons) will be drawn for routine tests and to check the immune system. Adverse events and medications taken will be reviewed on each cycle.Biomarkers will be taken on cycles 1, 2, 3, 6, and safety FU. Tumor Markers (special lab tests associated with the cancer, such as particular proteins) will be completed will be take on cycles 1, 4, 7, 10, 13, every 3 cycles and SFU.
Central lab tests will be completed on cycles 1, 2, 3, and 6 and safety FU. Cycle 1 Archived (prior stored) tumor sample will be obtained. Also, a liver tumor biopsy will be completed at Cycles 1, 3 and 6.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Criteria1, Participant provided informed consent prior to any study-specific activities/procedures.
- •Criteria 2, Confirmation of triple negative breast cancer or colorectal cancer with liver metastases by laboratory testing.
- •Criteria 3, Subjects with triple negative breast cancer with liver metastases, or subjects with colorectal cancer with liver metastases are eligible if they have had disease progression during or after one or more prior standard of care systemic anti-cancer therapy (eg,chemotherapy, targeted therapy) for metastatic disease or if they progress during or within 6 months of receiving adjuvant therapy. If subjects, in the opinion of the investigator, are deemed not appropriate candidates for systemic anti-cancer therapy for metastatic disease or if they refuse systemic anti-cancer therapy for metastatic disease, they may be eligible after investigator discussion with Sponsor medical monitor for approval.
- •Criteria 4, Participants have measurable disease which is equal to one or more metastatic liver lesions that can be accurately and serially measured that are greater than or equal to 1 cm dimension and for which the longest diameter is greater or equal to 1 cm as measured by CT (Computed Tomography) scan or magnetic resonance imaging. The metastatic liver lesion(s) must not be in an area that received prior localized therapies.
- •Criteria 5, Metastatic liver lesions for injection must be without necrosis (dead tissue )and must be be located where any tumor swelling will not lead to gall bladder tract obstruction or lead to bleeding risk.
- •Criteria 6, Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or
- •Criteria 7, Life expectancy greater than or equal to 5 months.
- •Criteria 8, Adequate organ function within 4 weeks prior to enrollment. This includes hematology, renal, hepatic and blood-clotting functions as defined by protocol.
- •Criteria 9, Female subjects of childbearing potential should have a negative serum pregnancy test within 1 week prior to enrollment.
- •Criteria 10, Other Inclusion Criteria May Apply.
排除标准
- •Criteria 1, Participant is a candidate for hepatic surgery or local regional therapy of liver metastases with curative intent.
- •Criteria 2, More than one third of the liver is estimated to be involved with metastases.
- •Criteria 3, There is invasion by cancer into the main blood vessels such as the portal vein, hepatic vein or the vena cava.
- •Criteria 4, Participant is currently receiving or has received liver metastatic-directed therapy ( eg: radiation, ablation, embolization) less than 4 wks prior to enrollment or hepatic surgery.
- •Criteria 5, History of other malignancy within the past 5 years prior to enrollment with some exceptions, as outlined in the protocol.
- •Criteria 6, Active or untreated central nervous system (CNS) metastases per CT or magnetic resonance imagine (MRI) evaluation during screening.
- •Participants with a history of CNS metastases are eligible provided they are stable and meet the criteria details in the protocol.
- •Criteria 7, Other Medical Conditions as noted in the protocol.
- •Criteria 8, Other Exclusion Criteria May Apply.
研究组 & 干预措施
Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)
Participants with CRC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
干预措施: Atezolizumab (Biological)
Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)
Participants with CRC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
干预措施: Talimogene Laherparepvec (Biological)
Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)
Participants with TNBC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
干预措施: Atezolizumab (Biological)
Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)
Participants with TNBC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
干预措施: Talimogene Laherparepvec (Biological)
结局指标
主要结局
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
时间窗: From Day 1 up to the start of Cycle 3 (each cycle is 21 days)
Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be related to either treatment: * Grade ≥ 4 neutropenia (absolute neutrophil count \[ANC\] \< 500/μl) lasting ≥ 7 days * Grade ≥ 3 febrile neutropenia * Grade ≥ 4 thrombocytopenia * Grade ≥ 4 anemia * Grade ≥ 4 rash * Serious herpetic events * Grade ≥ 3 symptomatic hepatic toxicities that do not resolve to Grade ≤ 2 within 48 hours or Grade ≥ 3 asymptomatic hepatic toxicities that do not resolve to Grade ≤ 1 within 3 weeks of onset * Grade ≥ 3 non-hematologic, non-hepatic organ toxicity * Grade 5 toxicity (ie, death) * Any other intolerable toxicity leading to permanent discontinuation of treatment DLTs were to occur within the DLT evaluation period, defined as the period between the initial 10\^6 PFU/mL dose and 3 weeks following the initial 10\^8 PFU/mL dose or the start of Cycle 3, whichever occurred first.
次要结局
- Disease Control Rate (DCR)(Every 12 weeks (± 28 days) up to approximately 3.5 years.)
- Lesion Level Response in Injected Tumor Lesions(Every 12 weeks (± 28 days) up to approximately 3.5 years.)
- Objective Response Rate (ORR)(Every 12 weeks (± 28 days) up to approximately 3.5 years.)
- Best Overall Response (BOR)(Every 12 weeks (± 28 days) up to approximately 3.5 years.)
- Duration of Response (DOR)(Every 12 weeks (± 28 days) up to approximately 3.5 years.)
- Lesion Level Response in Uninjected Tumor Lesions(Every 12 weeks (± 28 days) up to approximately 3.5 years.)
- Overall Survival (OS)(Every 12 weeks (± 28 days) up to approximately 3.5 years.)
- Durable Response Rate (DRR)(Every 12 weeks (± 28 days) up to approximately 3.5 years.)
- Progression-free Survival (PFS)(Every 12 weeks (± 28 days) up to approximately 3.5 years.)