Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
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).
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 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 Part 2.

 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,
 non-alcoholic fatty liver disease, 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.