Phase 1 Study of INBRX-109 in Subjects with Locally Advanced or Metastatic Solid Tumors Including Sarcomas
- Conditions
- Colorectal AdenocarcinomaEwing Sarcoma
- Interventions
- Registration Number
- NCT03715933
- Lead Sponsor
- Inhibrx Biosciences, Inc
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 321
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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.
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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 with locally advanced or metastatic, unresectable disease, who have received at least 2 but no more than 3 prior lines of systemic therapy.
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Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.
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Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
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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).
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Estimated life expectancy of at least 12 weeks.
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Availability of archival tissue or fresh cancer biopsy are mandatory.
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Prior treatment with or exposure to DR5 agonists.
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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.
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Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
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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.
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Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exceptions per protocol.
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Prior or concurrent malignancies. Exceptions per protocol.
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Hematologic malignancies.
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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.
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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.
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Acute viral or toxic liver disease within 12 months prior to the first dose of study drug.
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Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
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Known sensitivity or contraindications to the following drugs:
- Ewing sarcoma: irinotecan or TMZ
- colorectal adenocarcinoma: FU, leucovorin, or irinotecan
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Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease less than 3 months prior to enrollment.
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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.
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Major surgery within 4 weeks prior to enrollment on this trial.
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Systemic infection requiring antibiotics within 2 weeks prior to the first dose of study drug.
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Other exclusion criteria per protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Combination Expansion Pancreatic Adenocarcinoma (Complete) Irinotecan Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy Combination Expansion Ewing Sarcoma INBRX-109 Subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide Combination Expansion Ewing Sarcoma Irinotecan Subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide Combination Expansion Ewing Sarcoma Temozolomide Subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide Combination Expansion Colorectal Adenocarcinoma INBRX-109 Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy Combination Expansion Colorectal Adenocarcinoma 5-fluorouracil Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy Combination Expansion Colorectal Adenocarcinoma Irinotecan Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy Expansion Solid Tumors (Complete) INBRX-109 Subjects with Solid tumors and high BMI will be treated with single-agent INBRX-109 at either the MTD or RP2D. Combination Expansion SDH-deficient solid tumors or GIST (Complete) INBRX-109 Subjects with SDH-deficient solid tumors or GIST will be treated with INBRX-109 in combination with temozolomide Combination Expansion SDH-deficient solid tumors or GIST (Complete) Temozolomide Subjects with SDH-deficient solid tumors or GIST will be treated with INBRX-109 in combination with temozolomide Combination Expansion Pancreatic Adenocarcinoma (Complete) INBRX-109 Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy Combination Expansion Pancreatic Adenocarcinoma (Complete) 5-fluorouracil Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy Dose Escalation (Complete) INBRX-109 INBRX-109 will be escalated (3+3 design) in subjects with locally advanced or metastatic solid tumors including sarcomas. Expansion Malignant Pleural Mesothelioma (Complete) INBRX-109 Subjects with malignant pleural mesothelioma will be treated with single-agent INBRX-109 at either the MTD or RP2D. Expansion Gastric Adenocarcinoma (Complete) INBRX-109 Subjects with gastric adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D. Expansion Colorectal Adenocarcinoma (Complete) INBRX-109 Subjects with colorectal (CRC) adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D. Expansion Sarcomas (Complete) INBRX-109 Subjects with certain sarcoma subtypes will be treated with single-agent INBRX-109 at either the MTD or RP2D. Combination Expansion Malignant Pleural Mesothelioma (Complete) INBRX-109 Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed) Combination Expansion Malignant Pleural Mesothelioma (Complete) Carboplatin Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed) Combination Expansion Malignant Pleural Mesothelioma (Complete) Cisplatin Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed) Combination Expansion Malignant Pleural Mesothelioma (Complete) Pemetrexed Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed)
- Primary Outcome Measures
Name Time Method Frequency and severity of adverse events of INBRX-109 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 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.
- Secondary Outcome Measures
Name Time Method Characterize the pharmacokinetics of INBRX-109 as a single agent, and of INBRX-109 in combination with distinct chemotherapies. Up to 8 years A measurement which indicates how the body processes INBRX-109 and how long it stays in the system.
Median progression-free survival for colorectal adenocarcinoma and Ewing sarcoma. Up to 8 years Progression-free survival is defined as the time from start of study treatment until documented disease progression or death.
Immunogenicity of INBRX-109 Up to 8 years Frequency of ant-drug antibodies (ADA) against INBRX-109 will be determined.
Trial Locations
- Locations (34)
Precision NextGen Oncology and Research
🇺🇸Beverly Hills, California, United States
University of California, San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Children's Hospital of Philadelphia- Center for Childhood Cancer Research
🇺🇸Philadelphia, Pennsylvania, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Centre Leon Berard
🇫🇷Lyon, France
Gustave Roussy
🇫🇷Villejuif Cedex, France
La Fondazione e l'Istituto di Candiolo
🇮🇹Candiolo, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Great North Children's Hospital
🇬🇧London, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
HonorHealth Research Institute
🇺🇸Scottsdale, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
University of California, San Diego (UCSD) - Moores Cancer Center
🇺🇸San Diego, California, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Emory University - Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
The University of Chicago
🇺🇸Chicago, Illinois, United States
Center for Cancer Research at NCI
🇺🇸Bethesda, Maryland, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
START Midwest Michigan, PC
🇺🇸Grand Rapids, Michigan, United States
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Vanderbilt University School of Medicine
🇺🇸Nashville, Tennessee, United States
UT MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
NEXT Oncology - Virginia
🇺🇸Fairfax, Virginia, United States