Primary Outcome Measures
- Frequency and severity of adverse events of INBRX-109 [ Time Frame: Up to 2 years ]
Adverse events will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. - Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-109 [ Time Frame: Up to 2 years ] The MTD and/or RP2D of INBRX-109 will be determined.
Secondary Outcome Measures
- Area under the serum concentration time curve (AUC) of INBRX-109 [ Time Frame: Up to 2 years ]
Area under the serum concentration time curve (AUC) of INBRX-109 will be determined. - Immunogenicity of INBRX-109 [ Time Frame: Up to 2 years ]
Frequency of ant-drug antibodies (ADA) against INBRX-109 will be determined. - Maximum observed serum concentration (Cmax) of INBRX-109 [ Time Frame: Up to 2 years ]
Maximum observed serum concentration (Cmax) of INBRX-109 will be determined. - Trough observed serum concentration (Ctrough) of INBRX-109 [ Time Frame: Up to 2 years ]
Trough observed serum concentration (Cmax) of INBRX-109 will be determined. - Time to Cmax (Tmax) of INBRX-109 [ Time Frame: Up to 2 years ]
Time to Cmax (Tmax) of INBRX-109 will be determined.
- Inclusion Criteria
- 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 clinical
benefit - 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) 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.
- 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.
