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, two-part phase 1 trial of INBRX-109, which is a recombinant humanized multivalent antibody targeting the human death receptor 5 (DR5).

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.

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Source: the U.S. National Institutes of Health via ClinicalTrials.gov. Last updated: November 16th, 2018.

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Last update: January 19, 2018. 04:57:31 pm.