This is a first-in-human, open-label, non-randomized, two-part phase 1 trial of INBRX-109,
which is a recombinant humanized multivalent antibody targeting the human death receptor 5
- Part 1 Escalation: Histologically or cytologically-confirmed advanced/metastatic or
nonresectable 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
- Part 2 Expansion Cohorts: Malignant pleural mesothelioma, gastric adenocarcinoma and
colorectal adenocarcinoma 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)
- 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.
- 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
- 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
- Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
- 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