Clinical Trial Details
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
Overview
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).
Eligibility
| Ages | 12 Years - 85 Years |
| Sex | All |
| Healthy Volunteers | No |
| Age Groups | Child, Adult, Older Adult |
Inclusion Criteria:
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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 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.
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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.
Exclusion Criteria:
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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, irinotecan, bevacizumab or FTP/TPI
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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.
