An Open-Label, Multicenter, First-in-Human, Phase 1 Dose-Escalation and Multicohort Expansion Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 411
- 试验地点
- 63
- 主要终点
- Frequency and severity of adverse events of INBRX-109
研究概览
简要总结
This is a first-in-human, open-label, non-randomized, three-part phase 1 trial of INBRX-109, which is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).
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
- 12 Years 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females aged ≥12 to less than 85 years for Ewing sarcoma and 18 to less than 85 years of age for other tumors.
- •Part 3 combination therapy expansion tumor types:
- •Histologically confirmed Ewing sarcoma with a classical fusion: Patients with locally advanced or metastatic, unresectable, relapsed, or refractory disease who have received at least 1 but no more than 2 prior lines of systemic treatment with a preferred first line chemotherapy regimens.
- •Colorectal adenocarcinoma: Patients who have failed 1 (one) prior line of systemic therapy that did not include irinotecan.
- •Colorectal adenocarcinoma: Patients who have failed 2 but no more than 3 prior lines of systemic therapy and are FTD/TPI-naïve.
- •Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.
- •Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1, or Karnofsky Performance Status score of ≥60, or Lansky Play-Performance Scale for Children score ≥60 (for patients less than 16 years).
- •Estimated life expectancy of at least 12 weeks.
- •Availability of archival tissue or fresh cancer biopsy are mandatory.
排除标准
- •Prior treatment with or exposure to DR5 agonists.
- •Receipt of any anticancer therapy (including investigational agents) within 4 weeks or within 5 half-lives prior to the first dose of study treatment. Exceptions per protocol.
- •Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
- •Receipt of radiotherapy within 4 weeks prior to the first dose of study treatment, and liver-directed within 12 months prior to the first dose of study drug.
- •Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exceptions per protocol.
- •Prior or concurrent malignancies. Exceptions per protocol.
- •Hematologic malignancies.
- •Symptomatic active primary CNS tumors, leptomeningeal disease, and CNS metastases. Exceptions per protocol. Patients with any evidence or history of multiple sclerosis (MS) or other demyelinating disorders are excluded.
- •Chronic liver diseases including fatty liver. Exception: Patients < 45 years old with fatty liver disease may be accepted as long as adequate hepatic function as defined in the inclusion/exclusion criteria is confirmed.
- •Acute viral or toxic liver disease within 12 months prior to the first dose of study drug.
- •Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
- •Known sensitivity or contraindications to the following drugs:
- •Ewing sarcoma: irinotecan or TMZ
- •colorectal adenocarcinoma: FU, leucovorin, irinotecan, bevacizumab or FTP/TPI
- •Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease less than 3 months prior to enrollment.
- •Acute, hemodynamically significant deep vein thrombosis or clinically significant pulmonary embolism not resolved or stable for at least 3 months prior to the start of study treatment.
- •Major surgery within 4 weeks prior to enrollment on this trial.
- •Systemic infection requiring antibiotics within 2 weeks prior to the first dose of study drug.
- •Other exclusion criteria per protocol.
研究组 & 干预措施
Combination Expansion Colorectal Adenocarcinoma (Complete)
Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy
干预措施: Leucovorin (Drug)
Combination Expansion Colorectal Adenocarcinoma patients with FOLFIRI plus bevacizumab
Colorectal adenocarcinoma will be treated with INBRX-109 with FOLFIRI (FU, leucovorin, and irinotecan) plus bevacizumab
干预措施: Bevacizumab (Drug)
Combination Expansion Adolescent Ewing Sarcoma
Adolescent (12 to <18) subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide
干预措施: INBRX-109 (Drug)
Combination Expansion Adolescent Ewing Sarcoma
Adolescent (12 to <18) subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide
干预措施: Temozolomide (Drug)
Combination Expansion Adolescent Ewing Sarcoma
Adolescent (12 to <18) subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide
干预措施: Irinotecan (Drug)
Combination Expansion Colorectal Adenocarcinoma (Complete)
Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy
干预措施: Irinotecan (Drug)
Combination Expansion Colorectal Adenocarcinoma patients with FOLFIRI plus bevacizumab
Colorectal adenocarcinoma will be treated with INBRX-109 with FOLFIRI (FU, leucovorin, and irinotecan) plus bevacizumab
干预措施: Irinotecan (Drug)
Combination Expansion Adult Ewing Sarcoma
Adult subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide
干预措施: Temozolomide (Drug)
Combination Expansion Adult Ewing Sarcoma
Adult subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide
干预措施: INBRX-109 (Drug)
Expansion Colorectal Adenocarcinoma (Complete)
Subjects with colorectal (CRC) adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
干预措施: INBRX-109 (Drug)
Combination Expansion Pancreatic Adenocarcinoma (Complete)
Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy
干预措施: Irinotecan (Drug)
Combination Expansion Colorectal Adenocarcinoma with FTD/TPI plus bevacizumab
Colorectal adenocarcinoma will be treated with INBRX-109 with FTD/TPI plus bevacizumab
干预措施: INBRX-109 (Drug)
Combination Expansion Colorectal Adenocarcinoma with FTD/TPI plus bevacizumab
Colorectal adenocarcinoma will be treated with INBRX-109 with FTD/TPI plus bevacizumab
干预措施: Trifluridine + Tipiracil (Drug)
Combination Expansion Colorectal Adenocarcinoma (Complete)
Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy
干预措施: INBRX-109 (Drug)
Combination Expansion Colorectal Adenocarcinoma with FTD/TPI plus bevacizumab
Colorectal adenocarcinoma will be treated with INBRX-109 with FTD/TPI plus bevacizumab
干预措施: Bevacizumab (Drug)
Combination Expansion Pancreatic Adenocarcinoma (Complete)
Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy
干预措施: INBRX-109 (Drug)
Combination Expansion Colorectal Adenocarcinoma patients with FOLFIRI plus bevacizumab
Colorectal adenocarcinoma will be treated with INBRX-109 with FOLFIRI (FU, leucovorin, and irinotecan) plus bevacizumab
干预措施: INBRX-109 (Drug)
Combination Expansion Adult Ewing Sarcoma
Adult subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide
干预措施: Irinotecan (Drug)
Combination Expansion Colorectal Adenocarcinoma patients with FOLFIRI plus bevacizumab
Colorectal adenocarcinoma will be treated with INBRX-109 with FOLFIRI (FU, leucovorin, and irinotecan) plus bevacizumab
干预措施: Leucovorin (Drug)
Combination Expansion Colorectal Adenocarcinoma patients with FOLFIRI plus bevacizumab
Colorectal adenocarcinoma will be treated with INBRX-109 with FOLFIRI (FU, leucovorin, and irinotecan) plus bevacizumab
干预措施: Fluorouracil (Drug)
Combination Expansion Malignant Pleural Mesothelioma (Complete)
Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed)
干预措施: INBRX-109 (Drug)
Combination Expansion Colorectal Adenocarcinoma (Complete)
Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy
干预措施: Fluorouracil (Drug)
Combination Expansion Pancreatic Adenocarcinoma (Complete)
Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy
干预措施: Fluorouracil (Drug)
Combination Expansion SDH-deficient solid tumors or GIST (Complete)
Subjects with SDH-deficient solid tumors or GIST will be treated with INBRX-109 in combination with temozolomide
干预措施: Temozolomide (Drug)
Expansion Gastric Adenocarcinoma (Complete)
Subjects with gastric adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
干预措施: INBRX-109 (Drug)
Combination Expansion Malignant Pleural Mesothelioma (Complete)
Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed)
干预措施: pemetrexed (Drug)
Expansion Malignant Pleural Mesothelioma (Complete)
Subjects with malignant pleural mesothelioma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
干预措施: INBRX-109 (Drug)
Combination Expansion Malignant Pleural Mesothelioma (Complete)
Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed)
干预措施: carboplatin (Drug)
Dose Escalation (Complete)
INBRX-109 will be escalated (3+3 design) in subjects with locally advanced or metastatic solid tumors including sarcomas.
干预措施: INBRX-109 (Drug)
Combination Expansion SDH-deficient solid tumors or GIST (Complete)
Subjects with SDH-deficient solid tumors or GIST will be treated with INBRX-109 in combination with temozolomide
干预措施: INBRX-109 (Drug)
Expansion Sarcomas (Complete)
Subjects with certain sarcoma subtypes will be treated with single-agent INBRX-109 at either the MTD or RP2D.
干预措施: INBRX-109 (Drug)
Combination Expansion Pancreatic Adenocarcinoma (Complete)
Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy
干预措施: Leucovorin (Drug)
Expansion Solid Tumors (Complete)
Subjects with Solid tumors and high BMI will be treated with single-agent INBRX-109 at either the MTD or RP2D.
干预措施: INBRX-109 (Drug)
结局指标
主要结局
Frequency and severity of adverse events of INBRX-109
时间窗: Up to 8 years
Adverse events will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Evaluating Tumor Response for colorectal cancers and Ewing sarcoma
时间窗: Up to 8 years
Evaluating how the tumor responds to treatment by measuring the number of patients with colorectal cancer and Ewing sarcoma that experience tumor shrinkage and for how long.
次要结局
- Characterize the pharmacokinetics of INBRX-109 as a single agent, and of INBRX-109 in combination with distinct chemotherapies.(Up to 8 years)
- Median progression-free survival for colorectal adenocarcinoma and Ewing sarcoma.(Up to 8 years)
- Immunogenicity of INBRX-109(Up to 8 years)