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Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Keytruda (MK-3475-A31/KEYNOTE-A31) in Advanced or Metastatic Malignancy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04130542
Recruitment Status : Recruiting
First Posted : October 17, 2019
Last Update Posted : November 22, 2021
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Lyvgen Biopharma Holdings Limited

Tracking Information
First Submitted Date  ICMJE October 14, 2019
First Posted Date  ICMJE October 17, 2019
Last Update Posted Date November 22, 2021
Actual Study Start Date  ICMJE October 31, 2019
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2019)
Safety/Tolerability [ Time Frame: up to 24 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Keytruda (MK-3475-A31/KEYNOTE-A31) in Advanced or Metastatic Malignancy
Official Title  ICMJE An Open Label, First in Human (FIH), Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Pembrolizumab (MK-3475-A31/KEYNOTE-A31) in Advanced or Metastatic Malignancy
Brief Summary

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 (Pembrolizumab/MK-3475) 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 (MK-3475). 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 (MK-3475) 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE Biological: LVGN6051
IV infusion once every 3 weeks (Q3W).
Study Arms  ICMJE Experimental: LVGN6051
The 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.
Intervention: Biological: LVGN6051
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 15, 2019)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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: Lynn Jiang, PhD 1-484-686-9652
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04130542
Other Study ID Numbers  ICMJE LVGN6051-101
KEYNOTE-A31 ( Other Identifier: Merck Sharp & Dohme Corp. )
Has Data Monitoring Committee Not Provided
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 Not Provided
Responsible Party Lyvgen Biopharma Holdings Limited
Study Sponsor  ICMJE Lyvgen Biopharma Holdings Limited
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE Not Provided
PRS Account Lyvgen Biopharma Holdings Limited
Verification Date November 2021

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