Clinical Trials /

Study of INBRX-105 in Patients With Solid Tumors, Hodgkin or Non-Hodgkin Lymphoma

NCT03809624

Description:

This is a first-in-human, open-label, nonrandomized, two-part Phase 1 trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX-105. INBRX-105, a next generation bispecific antibody, targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. INBRX-105 provides immune checkpoint blockade of PD-L1 as well as conditional T cell co-stimulation through 4-1BB agonism for localized immune stimulation.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hodgkin Lymphoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Hodgkin Lymphoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of INBRX-105 in Patients With Solid Tumors, Hodgkin or Non-Hodgkin Lymphoma
  • Official Title: An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 Study of INBRX-105 in Patients With Locally Advanced or Metastatic Solid Tumors, Hodgkin or Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: Ph 1 INBRX-105
  • NCT ID: NCT03809624

Conditions

  • Metastatic Solid Tumors
  • Hodgkin Lymphoma
  • Non Hodgkin Lymphoma
  • Non-small Cell Lung Cancer
  • Melanoma
  • Head and Neck Squamous Cell Carcinoma
  • Gastric Adenocarcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
  • Esophageal Adenocarcinoma

Interventions

DrugSynonymsArms
INBRX-105 - PDL1x41BB antibodyPart 1 Escalation

Purpose

This is a first-in-human, open-label, nonrandomized, two-part Phase 1 trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX-105. INBRX-105, a next generation bispecific antibody, targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. INBRX-105 provides immune checkpoint blockade of PD-L1 as well as conditional T cell co-stimulation through 4-1BB agonism for localized immune stimulation.

Trial Arms

NameTypeDescriptionInterventions
Part 1 EscalationExperimentalINBRX-105 will be escalated in subjects with locally advanced or metastatic solid tumors, Hodgkin or Non-Hodgkin lymphoma.
  • INBRX-105 - PDL1x41BB antibody
Expansion Cohort Non-small Cell Lung CancerExperimentalSubjects will be treated with single-agent INBRX-105 at either the MTD or RP2D.
  • INBRX-105 - PDL1x41BB antibody
Expansion Cohort MelanomaExperimentalSubjects will be treated with single-agent INBRX-105 at either the MTD or RP2D.
  • INBRX-105 - PDL1x41BB antibody
Expansion Cohort PD-L1 BasketExperimentalSubjects with head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with single-agent INBRX-105 at either the MTD or RP2D.
  • INBRX-105 - PDL1x41BB antibody

Eligibility Criteria

        Inclusion Criteria:

          -  Part 1 (escalation): Patients with locally advanced or metastatic non-resectable solid
             tumors, Hodgkin or Non-Hodgkin lymphoma whose disease has progressed despite standard
             therapy and for whom no further standard therapy exists, or who refuse available
             standard treatment options.

          -  Part 2 (expansion cohorts): Patients with non-small cell lung cancer, melanoma, and
             PD-L1 basket cohort consisting of head and neck squamous cell carcinoma, gastric or
             gastro-esophageal junction adenocarcinoma, renal cell carcinoma, or urothelial
             (transitional) cell carcinoma, with locally advanced or metastatic, non-resectable
             disease, which has progressed despite standard therapy or for whom no standard or
             clinically acceptable therapy exists.

          -  Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE:
             Only for tumor types, for which these checkpoint inhibitors are FDA approved).

          -  PD-L1 positivity by immunohistochemistry (IHC). Part 1 (escalation) PD-L1 positivity
             is not required. Expansion cohorts: Combined Positive Score (CPS) or Tumor Proportion
             Score (TPS) ≥ 5%.

          -  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 exposure to 4-1BB agonists.

          -  Receipt of any investigational product or any approved anticancer drug(s) or
             biological product(s) within 4 weeks prior to the first dose of study drug.
             Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives. NOTE:
             Previous exposure to anti-PD-L1 checkpoint inhibitor requires a minimum washout period
             of 24 weeks prior to the first dose of study drug.

          -  Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, and multiple myeloma) other
             than lymphoma.

          -  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-105.

          -  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.

          -  Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation
             of prior immunotherapy. Some exceptions as defined per protocol apply.

          -  Active autoimmune disease or documented history of autoimmune disease that required
             systemic steroids or other immunosuppressive medications. Certain exceptions as
             defined in protocol apply.

          -  Treatment with systemic immunosuppressive medications within 4 weeks prior to the
             first dose of study drug. Certain exceptions as defined in protocol apply.

          -  History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
             for Part 1. Exceptions as defined in protocol for expansion cohorts will apply.

          -  History of hepatitis or cirrhosis (e.g., non-alcohol steatohepatitis, alcohol or
             drug-related, autoimmune, hepatitis B, or hepatitis C) for Part 1. Exceptions as
             defined in protocol for expansion cohorts will apply.

          -  Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or
             pneumonitis requiring treatment with steroids or other immunosuppressive medications.

          -  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.

          -  Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first
             dose of study drug.

          -  Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC)
             or bone marrow (BM) transplantation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency of adverse events of INBRX-105
Time Frame:Up to 2-3 years
Safety Issue:
Description:Adverse events will be assessed by 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-105
Time Frame:Up to 2-3 years
Safety Issue:
Description:Area under the serum concentration time curve (AUC) of INBRX-105 will be determined.
Measure:Maximum observed serum concentration (Cmax) of INBRX-105
Time Frame:Up to 2-3 years
Safety Issue:
Description:Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.
Measure:Trough observed serum concentration (Ctrough) of INBRX-105
Time Frame:Up to 2-3 years
Safety Issue:
Description:Trough observed serum concentration (Cmax) of INBRX-105 will be determined.
Measure:Time to Cmax (Tmax) of INBRX-105
Time Frame:Up to 2-3 years
Safety Issue:
Description:Time to Cmax (Tmax) of INBRX-105 will be determined.
Measure:Immunogenicity of INBRX-105
Time Frame:Up to 2-3 years
Safety Issue:
Description:Frequency of anti-drug antibodies (ADA) against INBRX-105 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
  • Hodgkin Lymphoma
  • Non Hodgkin Lymphoma
  • Lung Cancer
  • Melanoma
  • Head and Neck Cancer
  • Stomach Cancer
  • Gastric Cancer
  • Kidney Cancer
  • Renal cell carcinoma
  • Renal Cancer
  • Urothelial Carcinoma
  • PDL1
  • 41BB
  • PD-L1
  • 4-1BB

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