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

Phase 1

Completed

• Conditions: Cancer
• Interventions: Drug: LVGN6051; Drug: Pembrolizumab

• Registration Number: NCT04694781
• Lead Sponsor: Lyvgen Biopharma Holdings Limited

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-12-16
• Study First Submitted QC: 2021-01-04
• Study First Posted: 2021-01-05
• Study Start: 2021-05-14
• Primary Completion: 2023-10-31
• Study Completion: 2023-10-31
• Status Verified: 2024-03
• Last Update Submitted: 2024-04-18
• Last Update Posted: 2024-04-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Monotherapy Dose Escalation	LVGN6051	LVGN6051 monotherapy dose escalation
Combination therapy dose escalation	LVGN6051	LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose escalation
Combination therapy dose expansion	LVGN6051	LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose expansion cohorts
Monotherapy Dose Expansion	LVGN6051	LVGN6051 dose expansion cohorts
Combination therapy dose escalation	Pembrolizumab	LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose escalation
Combination therapy dose expansion	Pembrolizumab	LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose expansion cohorts

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
PK parameter Cmax	up to 24 months	Peak Plasma Concentration (Cmax) will be summarized.
ADA to LVGN6051	up to 24 months	The presence of ADA directed against LVGN6051 will be determined.
DCR	up to 24 months	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.
PK parameter AUC	up to 24 months	Area under the serum concentration versus time curve (AUC) will be determined.
PK parameter t1/2	up to 24 months	Serum concentration half-life t1/2 will be summarized.

Trial Locations

Locations (2)

Shanghai Chest Hospital; 🇨🇳 Shanghai, China

Cancer Hospital Chinese Academy of Medical Sciences; 🇨🇳 Beijing, China