Clinical Trials /

Phase 1 Trial of LVGN7409 (CD40 Agonist Antibody) as Single Agent and Combination Therapies in Advanced or Metastatic Malignancy

NCT04635995

Description:

LVGN7409 is a humanized monoclonal antibody that specifically binds to CD40, and acts as an agonist against CD40. This first in human study of LVGN7409 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 LVGN7409, both as a single agent (monotherapy) and in combination with a fixed dose of anti-PD-1 antibody and/or CD40 agonist in the treatment of advanced or metastatic malignancy.

Related Conditions:
  • Cancer
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Trial of LVGN7409 (CD40 Agonist Antibody) as Single Agent and Combination Therapies in Advanced or Metastatic Malignancy
  • Official Title: An Open Label, First in Human (FIH), Phase 1a/1b Trial of LVGN7409 (CD40 Agonist Antibody) as a Single Agent, in Combination With LVGN3616 (Anti-PD-1 Antibody), and in Combination With LVGN3616 and LVGN6051 (CD137 Agonist Antibody) in Patients With Locally Advanced, Relapsed, Refractory, or Metastatic Malignancy

Clinical Trial IDs

  • ORG STUDY ID: LVGN7409-101
  • NCT ID: NCT04635995

Conditions

  • Cancer

Interventions

DrugSynonymsArms
LVGN7409Monotherapy dose escalation

Purpose

LVGN7409 is a humanized monoclonal antibody that specifically binds to CD40, and acts as an agonist against CD40. This first in human study of LVGN7409 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 LVGN7409, both as a single agent (monotherapy) and in combination with a fixed dose of anti-PD-1 antibody and/or CD40 agonist 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 LVGN7409 as a single agent (monotherapy) and in combination with
      anti-PD-1 antibody and/or CD40 agonist. 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
      LVGN7409 or anti-PD-1 antibody and/or CD40 agonist 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
Monotherapy dose escalationExperimentalThe monotherapy dose escalation phase includes 8 dose levels of LVGN7409. 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.
  • LVGN7409

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:

          -  Prior therapy with anti-CD40 therapy.

          -  Receipt of systemic anticancer therapy or radiotherapy within certain period of time.

          -  Prior exposure to immune-therapeutics experienced Grade ≥ 3 drug-related toxicity, or
             a toxicity requiring discontinuation.

          -  Received a live-virus vaccine within 30 days of the first dose of study drug.

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

          -  History of Grade ≥ 3 immune-related AEs (irAEs).

          -  Prolonged QT syndrome, or clinically significant cardiac condition.

          -  Receiving an immunologically based treatment for any reason.

          -  History or current active or chronic autoimmune disease.

          -  Uncontrolled pleural effusion, pericardial effusion, or recurrent ascites drainage.

          -  Female patients who are pregnant or breastfeeding.

          -  History of hemorrhagic or ischemic stroke within the last 6 months.

          -  Previously received an allogeneic tissue/organ transplant, stem cell or bone marrow
             transplant or solid organ transplant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment-emergent adverse events (TEAEs)
Time Frame:up to 24 months
Safety Issue:
Description:determination of DLTs and serious AEs (SAEs) of LVGN7409 as monotherapy. Adverse events will be assessed, and severity will be assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Lyvgen Biopharma Holdings Limited

Trial Keywords

  • Lyvgen
  • CD40

Last Updated

November 19, 2020