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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Cancer

Intervention / Treatment
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* Drug: LVGN6051
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |