Study of LVGN6051 (CD137 Agonist Antibody) in Advanced or Metastatic Malignancy

An Open Label, Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Pembrolizumab in Advanced or Metastatic Malignancy

The study of LVGN6051-201 is designed to use a bridging dose escalation to quickly 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) in the treatment of advanced or metastatic malignancy.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: LVGN6051; Drug: Pembrolizumab

Detailed Description

Based on the dose escalation results from the study of LVGN6051-101, a bridging dose escalation (3+3) is used in study of LVGN6051-201. The 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. The first stage of the study is the single agent dose escalation and expansion phase (Part A). The second stage of the study is the combination dose escalation and expansion phase (Part B). 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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Cancer Hospital Chinese Academy of Medical Sciences
  • Shanghai, China
    • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Exclusion Criteria:

• Receipt of CD137 and or PD-1 antibodies.
• Receipt of systemic anticancer therapy within 5 half-lives 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.
• 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.
• Tested positive of HIV or HBV or HCV.
• Female patients who are pregnant or breastfeeding.
• Any evidence of severe or uncontrolled systemic disease.
• Has previously had a CAR-T therapy, or stem cell or bone marrow or solid organ transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy Dose Escalation; LVGN6051 monotherapy dose escalation	Drug: LVGN6051; 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.
Experimental: Monotherapy Dose Expansion; LVGN6051 dose expansion cohorts	Drug: LVGN6051; 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.
Experimental: Combination therapy dose escalation; LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose escalation	Drug: LVGN6051; 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.; Drug: Pembrolizumab; 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.
Experimental: Combination therapy dose expansion; LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose expansion cohorts	Drug: LVGN6051; 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.; Drug: Pembrolizumab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events (TEAEs) including determination of DLTs and serious AEs (SAEs)	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.	up to 24 months
MTD or RDE or RP2D	maximal tolerated dose, recommended dose for expansion or recommended phase 2 dose	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	DCR will be documented as the proportion of patients with best overall response of CR, PR, or stable disease (SD). DCR per RECIST v1.1, iRECIST, and Cheson/Lugano criteria.	up to 24 months
PK parameter AUC	Area under the serum concentration versus time curve (AUC) will be determined.	up to 24 months
PK parameter Cmax	Peak Plasma Concentration (Cmax) will be summarized.	up to 24 months
PK parameter t1/2	Serum concentration half-life t1/2 will be summarized.	up to 24 months
ADA to LVGN6051	The presence of ADA directed against LVGN6051 will be determined.	up to 24 months

Collaborators and Investigators

• Sponsor: Lyvgen Biopharma Holdings Limited
• Investigators: Study Director: Xin Luo, Lyvgen Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: January 4, 2021
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: LVGN6051-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No