Clinical Trials /

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

NCT03715933

Description:

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).

Related Conditions:
  • Colorectal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Malignant Pleural Mesothelioma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: Ph1 INBRX-109
  • NCT ID: NCT03715933

Conditions

  • Solid Tumors
  • Malignant Pleural Mesothelioma
  • Gastric Adenocarcinoma
  • Colorectal Adenocarcinoma
  • Sarcoma

Interventions

DrugSynonymsArms
INBRX-109 - multivalent DR5 agonist antibodyDose Escalation

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalINBRX-109 will be escalated (3+3 design) in subjects with locally advanced or metastatic solid tumors including sarcomas.
  • INBRX-109 - multivalent DR5 agonist antibody
Expansion Malignant Pleural MesotheliomaExperimentalSubjects with malignant pleural mesothelioma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
  • INBRX-109 - multivalent DR5 agonist antibody
Expansion Gastric AdenocarcinomaExperimentalSubjects with gastric adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
  • INBRX-109 - multivalent DR5 agonist antibody
Expansion Colorectal AdenocarcinomaExperimentalSubjects with colorectal (CRC) adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
  • INBRX-109 - multivalent DR5 agonist antibody

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency and severity of adverse events of INBRX-109
Time Frame:Up to 2 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Area under the serum concentration time curve (AUC) of INBRX-109
Time Frame:Up to 2 years
Safety Issue:
Description:Area under the serum concentration time curve (AUC) of INBRX-109 will be determined.
Measure:Immunogenicity of INBRX-109
Time Frame:Up to 2 years
Safety Issue:
Description:Frequency of ant-drug antibodies (ADA) against INBRX-109 will be determined.
Measure:Maximum observed serum concentration (Cmax) of INBRX-109
Time Frame:Up to 2 years
Safety Issue:
Description:Maximum observed serum concentration (Cmax) of INBRX-109 will be determined.
Measure:Trough observed serum concentration (Ctrough) of INBRX-109
Time Frame:Up to 2 years
Safety Issue:
Description:Trough observed serum concentration (Cmax) of INBRX-109 will be determined.
Measure:Time to Cmax (Tmax) of INBRX-109
Time Frame:Up to 2 years
Safety Issue:
Description:Time to Cmax (Tmax) of INBRX-109 will be determined.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Inhibrx, Inc.

Trial Keywords

  • Phase 1
  • Phase 1 Clinical Trial
  • Solid Tumors
  • Sarcoma
  • Pleural Mesothelioma
  • Stomach Cancer
  • Colorectal Cancer
  • Colon Cancer
  • Rectal Cancer
  • DR5
  • Gastric Adenocarcinoma
  • Colorectal Adenocarcinoma

Last Updated