Clinical trial NCT04694781: Study of LVGN6051 (CD137 Agonist Antibody) in Advanced or Metastatic Malignancy
Official title: An Open Label, Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Pembrolizumab in Advanced or Metastatic Malignancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: Lyvgen Biopharma Holdings Limited
Sponsor class: INDUSTRY
First posted: 2021-01-05
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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.

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.

Primary outcomes:
measure: Treatment-emergent adverse events (TEAEs) including determination of DLTs and serious AEs (SAEs)
timeFrame: up to 24 months
measure: MTD or RDE or RP2D
timeFrame: up to 24 months
Secondary outcomes:
measure: DCR
timeFrame: up to 24 months
measure: PK parameter AUC
timeFrame: up to 24 months
measure: PK parameter Cmax
timeFrame: up to 24 months
measure: PK parameter t1/2
timeFrame: up to 24 months
measure: ADA to LVGN6051
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Shanghai
country: China
facility: Shanghai Chest Hospital
Study officials:
affiliation: Lyvgen Biopharma
name: Xin Luo
role: STUDY_DIRECTOR
References: