Clinical Trials /

Phase 1 Trial of LVGN6051 as Single Agent and in Combination Therapy in Advanced or Metastatic Malignancy

NCT04130542

Description:

LVGN6051 is a humanized monoclonal antibody that specifically binds to CD137, and acts as an agonist against CD137. This first in human study of LVGN6051 is designed to establish the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE) as well as the recommended Phase 2 dose(s) (RP2D) of LVGN6051, both as a single agent (monotherapy) and in combination with a fixed dose of anti-PD-1 antibody in the treatment of advanced or metastatic malignancy.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Trial of LVGN6051 as Single Agent and in Combination Therapy in Advanced or Metastatic Malignancy
  • Official Title: An Open Label, First in Human (FIH), Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Keytruda (Pembrolizumab) in Advanced or Metastatic Malignancy

Clinical Trial IDs

  • ORG STUDY ID: LVGN6051-101
  • NCT ID: NCT04130542

Conditions

  • Cancer

Interventions

DrugSynonymsArms
LVGN6051LVGN6051

Purpose

LVGN6051 is a humanized monoclonal antibody that specifically binds to CD137, and acts as an agonist against CD137. This first in human study of LVGN6051 is designed to establish the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE) as well as the recommended Phase 2 dose(s) (RP2D) of LVGN6051, both as a single agent (monotherapy) and in combination with a fixed dose of anti-PD-1 antibody in the treatment of advanced or metastatic malignancy.

Detailed Description

      This is an open-label, non-randomized, two-stage, FIH Phase 1 study, utilizing an accelerated
      dose escalation followed by a traditional 3 + 3 dose escalation algorithm to identify the MTD
      and/or RDE and RP2D of LVGN6051 as a single agent (monotherapy) and in combination with
      pembrolizumab (Keytruda). The first stage of the study is the dose escalation phase (i.e.,
      Phase 1a). The second stage of the study is the dose expansion phase (i.e., Phase 1b). During
      the study, dose interruption(s) and/or delay(s) may be implemented based on toxicity. Dose
      modifications are not permitted. Intra-patient dose escalations will be allowed for the early
      dose cohorts (single-patient dose groups) in Phase 1a Part 1. Patients will be considered
      evaluable for safety and tolerability if they receive at least one dose of LVGN6051 or
      pembrolizumab at the specified cohort dose. Patients in all parts of the trial will remain on
      therapy until confirmed disease progression or for 2 years, whichever occurs first. However,
      patients who are clinically unstable will discontinue following the initial assessment of
      disease progression.
    

Trial Arms

NameTypeDescriptionInterventions
LVGN6051ExperimentalThe dose escalation phase includes 10 dose levels of LVGN6051, and the highest dose is up to 10mg/kg. Route of administration is IV infusion, and the frequency of administration is once every 3 weeks (Q3W). one cycle is 3 weeks, and treatment can be up to 35 cycles if patients receive benefits.
  • LVGN6051

Eligibility Criteria

        Inclusion Criteria:

          -  Males or females aged ≥ 18 years.

          -  Ability to understand and willingness to sign a written informed consent document.

          -  Patients must have a histologically or cytologically confirmed metastatic or
             unresectable malignancy.

          -  Estimated life expectancy, in the judgment of the Investigator, of at least 90 days.

          -  Adequate bone marrow, liver, and renal functions.

          -  Men and women of childbearing potential must agree to take highly effective
             contraceptive methods.

          -  Patients should recover from all reversible AEs of previous anticancer therapies to
             baseline.

          -  Patients infected with the HIV virus will be eligible if the disease is under control
             of effective therapy.

        Exclusion Criteria:

          -  Receipt of systemic anticancer therapy including investigational agents or devices
             within 5 half-lives of the first dose of study treatment.

          -  Previous radiotherapy within 14 days of the first dose of study treatment.

          -  Known active CNS metastasis and/or carcinomatous meningitis.

          -  Has received a live-virus vaccine within 30 days.

          -  Has had a Grade ≥ 3 allergic reaction to treatment with a monoclonal antibody.

          -  Abnormality of QT interval or syndrome.

          -  Patients with history of Grade ≥ 3 immune-related AEs (irAEs) or irAE.

          -  Patients who are receiving an immunologically-based treatment for any reason.

          -  Treatment with systemic immune-stimulatory agents within 4 weeks prior to the first
             dose of study drug.

          -  Active or chronic autoimmune disease that has required systemic treatment in the past
             2 years or who are receiving systemic therapy for an autoimmune or inflammatory
             disease.

          -  Has a clinically significant cardiac condition, including unstable angina, acute
             myocardial infarction within 6 months.

          -  Has an active infection requiring intravenous (i.v.) anti-infectives within 14 days
             before the first dose of study treatment.

          -  Current evidence or history of interstitial lung disease or active, noninfectious
             pneumonitis requiring treatment such as oral or intravenous glucocorticoids to assist
             with management.

          -  Female patients who are pregnant or breastfeeding.

          -  Any evidence of severe or uncontrolled systemic disease.

          -  Any other disease or clinically significant abnormality in laboratory parameters.

          -  Has previously had a stem cell or bone marrow or solid organ transplant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety/Tolerability
Time Frame:up to 24 months
Safety Issue:
Description:mEvaluate the safety and tolerability and determine the Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) and recommended Phase 2 dose(s) (RP2D) of LVGN6051 administered as a single agent (monotherapy) and in combination with pembrolizumab, in adult patients with advanced malignancy.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Lyvgen Biopharma Holdings Limited

Last Updated

November 4, 2019