An Open-Label, Multicenter, First-in-Human, Dose-Escalation Phase 1 Study of INBRX-109 in Subjects with Locally Advanced or Metastatic Solid Tumors Including Sarcomas

Eligibility: Inclusion Criteria
  •   Escalation: Histologically or cytologically-confirmed advanced/metastatic or non-resectable solid tumors, including sarcoma, that are refractory or intolerant to standard therapy, or for which no standard therapy exists that is likely to confer any clinical benefit.
  •   Expansion Cohorts: Malignant pleural mesothelioma, gastric adenocarcinoma, colorectal adenocarcinoma, pancreatic adenocarcinoma and certain sarcoma subtypes (e.g., chondrosarcoma, Ewing sarcoma) with locally advanced or metastatic, non-resectable disease, that are refractory or intolerant to standard therapy, or for which no standard therapy exists that is likely to confer any clinical benefit.
  •   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) of 0 or 1 for Part 1 and ECOG PS of 0, 1 or 2 for Parts 2 and 3.
Exclusion Criteria
  •   Prior treatment with or exposure to DR5 agonists.
  •   Receipt of investigational agents or devices, anticancer therapy and radiotherapy (with the exception of palliative localized radiation) within 4 weeks prior to the first dose of study drug, and liver-directed therapies (i.e., RFA, TACE/embolization, cryotherapy, SBRT) within 12 weeks prior to the first dose of study drug. Exceptions per protocol.
  •   Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exception: Participants who have had a stem cell or bone marrow transplant > 5 years ago are eligible for enrollment, as long as there are no symptoms of graft-versus-host disease (GVHD).
  •   Prior or concurrent malignancies. Exception: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of INBRX-109.
  •   Hematologic malignancies.
  •   Known or active primary central nervous system (CNS) tumors, leptomeningeal disease and CNS metastases. Exception: Subjects with previously treated, asymptomatic, and clinically stable CNS metastases may be allowed study entry if certain criteria apply.
  •   Subjects with chronic liver diseases including but not limited to cirrhosis, NASH, alcohol-related liver disease, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, hepatic or biliary autoimmune disorders (i.e., primary biliary cholangitis, autoimmune hepatitis).
  •   Acute viral or toxic liver disease within 4 weeks prior to the first dose of study drug.
  •   Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
  •   Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease 3 months; left ventricular ejection fraction (LVEF) 50%; New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension. Active, hemodynamically significant pulmonary embolism within 3 months prior to enrollment on this trial.
  •   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.
  •   Part 3: Sensitivity or contraindications to carboplatin, cisplatin, pemetrexed, fluorouracil, irinotecan, or temozolomide.