Clinical Trials /

Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

NCT04198766

Description:

This is a first-in-human, open-label, non-randomized, 4-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 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda).

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of INBRX-106 in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
  • Official Title: An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 Study of INBRX 106 in Subjects With Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: Ph 1 INBRX-106
  • NCT ID: NCT04198766

Conditions

  • Solid Tumor
  • Non-Small Cell Lung Cancer
  • Melanoma
  • Head and Neck Cancer
  • Gastric Cancer
  • Renal Cell Carcinoma
  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
INBRX-106 - Hexavalent OX40 agonist antibodyPart 1 INBRX-106 Escalation
PembrolizumabKeytrudaPart 3 INBRX-106 Escalation in Combination with Pembrolizumab

Purpose

This is a first-in-human, open-label, non-randomized, 4-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 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda).

Trial Arms

NameTypeDescriptionInterventions
Part 1 INBRX-106 EscalationExperimentalINBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.
  • INBRX-106 - Hexavalent OX40 agonist antibody
Part 2 INBRX-106 ExpansionExperimentalSubjects with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-106 at the RP2D.
  • INBRX-106 - Hexavalent OX40 agonist antibody
Part 3 INBRX-106 Escalation in Combination with PembrolizumabExperimentalINBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors.
  • INBRX-106 - Hexavalent OX40 agonist antibody
  • Pembrolizumab
Part 4 INBRX-106 Expansion in Combination with PembrolizumabExperimentalSubjects with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-106 at the RP2D in combination with pembrolizumab.
  • INBRX-106 - Hexavalent OX40 agonist antibody
  • Pembrolizumab

Eligibility Criteria

        Select Inclusion Criteria:

          -  Males or females aged ≥18 years.

          -  Parts 1 and 3 (dose escalation): Subjects with locally advanced or metastatic non
             resectable solid tumors, whose disease has progressed despite all standard therapies
             or for whom no further standard or clinically acceptable therapy exists.

          -  Part 2 (single-agent expansion cohort): Subjects with NSCLC, melanoma, HNSCC, G/GEA,
             RCC, or TCC, with locally advanced or metastatic, non-resectable disease, which has
             progressed despite all standard therapies or for whom no standard or clinically
             acceptable therapy exists.

          -  Part 4 (pembrolizumab combination expansion cohorts): Subjects with melanoma, HNSCC,
             G/GEA, RCC, or TCC (Cohort F1) or NSCLC (Cohorts F2 and F3), with locally advanced or
             metastatic, non resectable disease, which has progressed despite all standard
             therapies or for whom no standard or clinically acceptable therapy exists.

          -  All subjects with non-squamous NSCLC must have documentation of absence of tumor
             activating EGFR mutations and absence of ALK gene rearrangements.

          -  PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional. Part 2: IHC result mandatory but any
             score allowed. Part 4: Combined Positive Score (CPS) ≥ 5%.

          -  Adequate hematologic, coagulation, hepatic and renal function and ECOG score as
             defined per protocol.

        Select Exclusion Criteria:

          -  Prior exposure to OX40 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 with
             certain exceptions.

          -  Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's lymphoma and
             multiple myeloma)

          -  Sarcomas

          -  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-106.

          -  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 Parts 1 and 3. 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-106 as single agent and in combination with pembrolizumab
Time Frame:2-4 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-106
Time Frame:2-4 years
Safety Issue:
Description:Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
Measure:Maximum observed serum concentration (Cmax) of INBRX-106
Time Frame:2-4 years
Safety Issue:
Description:Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
Measure:Trough observed serum concentration (Ctrough) of INBRX-106
Time Frame:2-4 years
Safety Issue:
Description:Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
Measure:Time to Cmax (Tmax) of INBRX-106
Time Frame:2-4 years
Safety Issue:
Description:Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
Measure:Immunogenicity of INBRX-106
Time Frame:2-4 years
Safety Issue:
Description:Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab 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
  • Melanoma
  • Head and Neck Cancer
  • Stomach Cancer
  • Gastric Cancer
  • Lung Cancer
  • Non-Small Cell Lung Cancer
  • Kidney Cancer
  • Renal Cell Carcinoma
  • Bladder Cancer
  • Urothelial Carcinoma
  • OX40
  • PD-1
  • Pembrolizumab
  • Keytruda

Last Updated

December 11, 2019