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Study of INBRX-105 in Patients With Solid Tumors (PDL1x41BB)

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ClinicalTrials.gov Identifier: NCT03809624
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : July 22, 2021
Sponsor:
Information provided by (Responsible Party):
Inhibrx, Inc.

Tracking Information
First Submitted Date  ICMJE January 15, 2019
First Posted Date  ICMJE January 18, 2019
Last Update Posted Date July 22, 2021
Actual Study Start Date  ICMJE January 30, 2019
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
  • Frequency of adverse events of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
  • Severity of adverse events of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Severity of adverse events will be assessed and assigned by 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-105 [ Time Frame: Up to 2-3 years ]
    The MTD and/or RP2D of INBRX-105 will be determined.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
  • Area under the serum concentration time curve (AUC) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Area under the serum concentration time curve (AUC) of INBRX-105 will be determined.
  • Maximum observed serum concentration (Cmax) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.
  • Trough observed serum concentration (Ctrough) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Trough observed serum concentration (Cmax) of INBRX-105 will be determined.
  • Time to Cmax (Tmax) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Time to Cmax (Tmax) of INBRX-105 will be determined.
  • Immunogenicity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Frequency of anti-drug antibodies (ADA) against INBRX-105 will be determined.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
  • Area under the serum concentration time curve (AUC) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Area under the serum concentration time curve (AUC) of INBRX-105 will be determined.
  • Maximum observed serum concentration (Cmax) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.
  • Trough observed serum concentration (Ctrough) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Trough observed serum concentration (Cmax) of INBRX-105 will be determined.
  • Time to Cmax (Tmax) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Time to Cmax (Tmax) of INBRX-105 will be determined.
  • Immunogenicity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Frequency of ant-drug antibodies (ADA) against INBRX-105 will be determined.
Current Other Pre-specified Outcome Measures
 (submitted: April 21, 2020)
  • Anti-tumor activity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
  • Anti-tumor activity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).
Original Other Pre-specified Outcome Measures
 (submitted: January 16, 2019)
  • Anti-tumor activity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Tumor response will be determined by RECISTv1.1.
  • Anti-tumor activity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Tumor response will be determined by iRECIST.
  • Anti-tumor activity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Tumor response will be determined by RECIL 2017 if applicable.
 
Descriptive Information
Brief Title  ICMJE Study of INBRX-105 in Patients With Solid Tumors
Official Title  ICMJE An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 Study of INBRX-105 and INBRX-105 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Brief Summary This is a first-in-human, open-label, nonrandomized, four-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 and INBRX-105 in combination with Pembrolizumab. 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 localized conditional T-cell co-stimulation through 4-1BB agonism.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Solid Tumors
  • Non-small Cell Lung Cancer
  • Melanoma
  • Head and Neck Squamous Cell Carcinoma
  • Gastric Adenocarcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
  • Esophageal Adenocarcinoma
Intervention  ICMJE
  • Drug: INBRX-105 - PDL1x41BB antibody
    The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.
  • Drug: Pembrolizumab
    Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
    Other Name: Keytruda
Study Arms  ICMJE
  • Experimental: Single Agent Escalation
    INBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors.
    Intervention: Drug: INBRX-105 - PDL1x41BB antibody
  • Experimental: Expansion Cohort Non-small Cell Lung Cancer
    Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.
    Intervention: Drug: INBRX-105 - PDL1x41BB antibody
  • Experimental: Expansion Cohort Melanoma
    Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.
    Intervention: Drug: INBRX-105 - PDL1x41BB antibody
  • Experimental: Expansion Cohort PD-L1 Positive Basket
    Patients with 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.
    Intervention: Drug: INBRX-105 - PDL1x41BB antibody
  • Experimental: Expansion Cohort Head and Neck Squamous Cell Carcinoma
    Patients with head and neck squamous cell carcinoma will be treated with single-agent INBRX-105 at either the MTD or RP2D.
    Intervention: Drug: INBRX-105 - PDL1x41BB antibody
  • Experimental: INBRX-105 Escalation in Combination with Pembrolizumab
    INBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors.
    Interventions:
    • Drug: INBRX-105 - PDL1x41BB antibody
    • Drug: Pembrolizumab
  • Experimental: Combination Expansion Cohort Non-small Cell Lung Cancer
    Patients will be treated with INBRX-105 in combination with Pembrolizumab.
    Interventions:
    • Drug: INBRX-105 - PDL1x41BB antibody
    • Drug: Pembrolizumab
  • Experimental: Combination Expansion Cohort Melanoma
    Patients will be treated with INBRX-105 in combination with Pembrolizumab.
    Interventions:
    • Drug: INBRX-105 - PDL1x41BB antibody
    • Drug: Pembrolizumab
  • Experimental: Combination Expansion Cohort Cohort PD-L1 Positive Basket
    Patients with head and neck squamous cell carcinoma, gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-105 in combination with Pembrolizumab.
    Interventions:
    • Drug: INBRX-105 - PDL1x41BB antibody
    • Drug: Pembrolizumab
  • Experimental: Combination Expansion Cohort Treatment Naive Non-small Cell Lung Cancer
    Treatment naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab.
    Interventions:
    • Drug: INBRX-105 - PDL1x41BB antibody
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2021)
170
Original Estimated Enrollment  ICMJE
 (submitted: January 16, 2019)
90
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Parts 1 and 3 (escalation cohorts): Patients with locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite standard therapy and for whom no further standard therapy exists.
  • Parts 2 and 4 (expansion cohorts): Patients with non-small cell lung cancer, melanoma, 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.
  • Part 4 treatment naive NSCLC cohort: Locally advanced or metastatic, non-resectable NSCLC, who have not received prior systemic treatment, including CPI, for advanced or metastatic disease. PD-L1 IHC Tumor Proportion Score (TPS) ≥ 1% and < 50%. In Part 4, all patients with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements.
  • Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE: For all tumor types with checkpoint inhibitor approvals) with exception of the treatment naive NSCLC cohort.
  • PD-L1 positivity by immunohistochemistry (IHC): Parts 1 and 3 (escalation cohorts) PD-L1 positivity is not required. Parts 2 and 4 (expansion cohorts): Combined Positive Score (CPS) or Tumor Proportion Score (TPS) above certain thresholds as defined per protocol.
  • Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.

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, NHL, Hodgkin lymphoma and multiple myeloma).
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Terri Boyea, Director Clin Ops 858-500-7833 terri@inhibrx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03809624
Other Study ID Numbers  ICMJE Ph 1 INBRX-105
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Inhibrx, Inc.
Study Sponsor  ICMJE Inhibrx, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Klaus Wagner, MD, PhD Inhibrx, Inc.
PRS Account Inhibrx, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP