An Open-Label, Multicenter, First-in-Human, Phase I Dose-Escalation and Multicohort Expansion Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
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Study Summary
To study INBRX-109 in patients with locally advanced or metastatic solid tumors including sarcomas To determine the safety of INBRX-109 in humans, as well as the recommended therapeutic dose level for future clinical development To initiate an Ewing sarcoma expansion cohort to explore the combination of INBRX-109 with irinotecan and temozolomide (IT) To evaluate the safety and efficacy of INBRX-109 in a variety of tumor types In these expansion cohorts, safety, PK, immunogenicity, efficacy and potential predictive diagnostic biomarkers of INBRX-109 are being evaluated To study the safety/tolerability of TMZ+INBRX-109 in patients with aggressive SDH-def cancers, including GIST
This is a phase I/II therapeutic exploratory and confirmatory clinical trial for safety and efficacy where only Phase 2 will be conducted in the EU. In line with EMA guidance on disclosure rules, this study is a category 2 trial
The main objective is to assess the safety and effectiveness of the drug, INBRX-109, given intravenously together with common chemotherapies in subjects with Ewing sarcoma, colorectal cancers and subjects with solid tumours (including gastrointestinal tract cancer (GIST)) that are deficient in a protein called SDH. Enrolment is closed for subjects with SDH-deficient solid tumours and GIST
- 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 with locally advanced or metastatic, unresectable disease, who have received at least 2 but no more than 3 prior lines of systemic therapy.
- 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.
- 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, or irinotecan
- 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.
Clinical Study Information for Healthcare Providers
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