An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase I/II Study of INBRX-105 and INBRX-105 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Study Identifier:
Ph1-2 INBRX-105
CT.gov Identifier:
NCT03809624
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Terminated/Withdrawn

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Study Summary

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 in locally advanced or metastatic solid tumors

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
  • Non-Small Cell Lung Cancer
  • Melanoma
  • Head & Neck
  • Gastric
  • Renal
  • Esophageal
  • Oral cavity and pharynx
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Single Agent Escalation
    • Read More
  • Drug: Experimental: Expansion Cohort Non-small Cell Lung Cancer
  • Drug: Experimental: Expansion Cohort Melanoma
  • Drug: Experimental: Expansion Cohort PD-L1 Positive Basket
  • Drug: Experimental: Expansion Cohort Nasopharyngeal or Oropharyngeal Carcinoma
  • Drug: Experimental: INBRX-105 Escalation in Combination with Pembrolizumab
  • Drug: Drug: Pembrolizumab
  • Drug: Experimental: Combination Expansion Cohort Non-small Cell Lung Cancer
  • Drug: Experimental: Combination Expansion Cohort Melanoma
  • Drug: Experimental: Combination Expansion Cohort Cohort PD-L1 Positive Basket
  • Drug: Experimental: Combination Expansion Cohort CPI Naive Non-small Cell Lung Cancer
  • Drug: Experimental: Combination Expansion Cohort CPI Naive HNSCC
  • Drug: Part 1, single agent dose escalation, was completed with a total of 32 patients enrolled.
  • Drug: Part 2, single agent dose expansion, began enrolling during the first quarter of 2021. Part 2 is enrolling between 62 to 98 patients in expansion cohorts in
  • Drug: Part 3, dose escalation of INBRX-105 in combination with Keytruda, enrolled 30 patients. These patients were not pre-screened for PD-L1 expression.
  • Drug: Part 4 of this trial, INBRX-105 in combination with Keytruda, is enrolling between 105 to 175 patients. Certain patients will be positive for PD-L1
  • Drug: Dose escalation (part 1, INBRX-105 single agent; part 3, combination) was completed. INBRX-105 is being assessed in dose-expansion cohorts (part 2, INBRX-105 single agent; part 4, combination).
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Terminated/Withdrawn

    Requirements information
    Inclusion criteria
    • Parts 1 and 3 (escalation cohorts; completed): 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.
    • Part 2 (expansion cohorts): Patients with non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma or solid tumors amenable to paired biopsies, 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 relapsed or refractory to CPI cohorts: NSCLC, cutaneous melanoma, HNSCC, MSI/TMB-high or MMRd solid tumors
    • Part 4 CPI naive cohorts: locally advanced or metastatic, non-resectable NSCLC or HNSCC
    • 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.
    • Patients naive to 4–1BB agonists with disease that progressed despite standard therapy or who have no alternative treatment options (except checkpoint inhibitor [CPI]-naive cohorts) were included.
    • Part 2a (recommended phase 2 dose [RP2D] expansion) consists of 4 cohorts: non-small cell lung cancer (NSCLC; PD-L1+), melanoma/solid tumors, head and neck squamous cell carcinoma (HNSCC), and other solid tumors (PD-L1+). Part 2b includes PD-L1-high HNSCC (including nasopharyngeal carcinoma). All part 2 cohorts, except melanoma (noncutaneous)/solid tumors, were CPI relapsed/refractory. PD-L1+ NSCLC (part 2a) and PD-L1-high HNSCC (part 2b) cohorts were opened based on encouraging early single-agent activity
    • Part 4 consists of CPI-relapsed/refractory cohorts (PD-L1+ NSCLC, cutaneous melanoma, PD-L1+ HNSCC, microsatellite instability-/tumor mutation burden-high or mismatch repair-deficient solid tumors) and CPI-naive cohorts (PDL1+ NSCLC and HNSCC). PD-L1 immunohistochemistry scores are required in parts 2 and 4, with threshold scores defined per protocol.
    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 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 PBSC/BM transplantation.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Manish Sharma
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Non-Small Cell Lung Cancer
    Melanoma
    Head & Neck
    Gastric
    Renal
    Esophageal
    Oral cavity and pharynx