Study of LVGN7409 (CD40 Agonist Antibody) in Locally Advanced, Metastatic or Recurrent/Refractory Malignancy

NCT05152212 | Completed Phase 1

• 1 other identifier: LVGN7409-201
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The study of LVGN7409-201 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 LVGN7409 as a single agent (monotherapy) in the treatment of locally advanced, metastatic or recurrent/refractory malignancy.

Conditions

Cancer

Outcome Measures

Primary Outcomes (3)

• MTD and/or RDE and RP2D

  MTD or RDE or RP2D will be determined according to safety, tolerability, Pharmacokinetic (PK) profile and clinical activity.

  up to 24 months

• Incidence rate of Dose-limiting Toxicity (DLT) within 3 weeks after first dose

  Incidence rate of dose-limiting toxicities within 3 weeks after first dose

  up to 24 months

• Safety and tolerability (Serious adverse events, adverse events, dose-limiting toxicities, Maximum Tolerated Dose)

  Adverse events will be assessed, and severity will be assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (ECI CTCAE) v5.0.

  up to 24 months

Secondary Outcomes (10)

• Objective Response Rate (ORR)

  up to 24 months

• Disease Control Rate (DCR)

  up to 24 months

• Duration of Respons (DOR)

  up to 24 months

• PK parameter

  up to 24 months

• PK parameter

  up to 24 months

Other Outcomes (3)

• Biomarkers PD-L1/ MSI/dMMR and/or tumor mutational burden (TMB)

  up to 24 months

• Biomarkers IL-6, IL-12, TNF-α, IFN-γ and soluble CD40 antigen

  up to 24 months

• Immune cell typing in peripheral blood, CD40 receptor occupation in B lymphocyte cell.

  up to 24 months

Study Arms (1)

LVGN7409

EXPERIMENTAL

Monotherapy Dose Escalation

Biological: LVGN7409

Interventions

LVGN7409 BIOLOGICAL

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.

LVGN7409

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged ≥ 18 years.
• Ability to understand and willingness to sign a written informed consent document (ICF).
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Estimated life expectancy, in the judgment of the Investigator, of at least 90 days.
• Adequate bone marrow function, as defined by all of the following:
• hemoglobin (Hb) ≥ 9.0 g/dL, and
• absolute neutrophil count (ANC) ≥ 1.5x10 9/L, and
• platelet count (PLT) ≥ 75x10 9/L.
• Adequate liver function, as defined by all of the following:
• Total bilirubin ≤ 1.5 × ULN; or ≤ 2.5 × ULN for patients who have serum bilirubin increases due to underlying Gilbert's Syndrome or familial benign unconjugated hyperbilirubinemia.
• Aspartate Aminotransferase (AST) ≤ 1.5 × ULN, and Alanine Transaminase (ALT) ≤ 1.5× ULN.
• International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT)- ≤1.5 × ULN unless participant is receiving anticoagulant therapy and levels are within the therapeutic range.
• Amylase and lipase ≤1.5 × ULN
• Adequate renal function as defined by an estimated serum creatinine clearance of ≥ 50 mL/min (calculated by Cockcroft-Gault formula) .
• Women of childbearing potential must agree to abstain from heterosexual intercourse or use highly effective contraceptive methods from the time of signing informed consent and through 120 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she (or her partner) is participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Prior therapy with anti-CD40 therapy including Bispecific antibody.
• Receipt of systemic anticancer therapy including investigational agents or devices within 5 half-lives of the first dose of study treatment. For anticancer therapies with half-life greater than 5 days, a washout of 21 days or longer is acceptable
• The subject was experienced radiotherapy within 14 days before the first dose of study treatment. \[Previous radiotherapy to the central nervous system (CNS) within 28 days of the first dose of study treatment\].
• Prior exposure to immune-therapeutics is allowed, including PD-1 and PD-L1 inhibitors, provided the participant did not experience Grade ≥ 3 drug-related toxicity, or a toxicity requiring discontinuation of the PD-1 or PD-L1 inhibitor.
• Known unstable CNS metastasis and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically and radiographically stable, without evidence of recurrence/progression, have no evidence of new or enlarging brain metastases or encephaledema, and are using no corticosteroids for at least 7 days prior to study medication.
• Received a live-virus vaccine within 30 days of the first dose of study drug.
• Grade ≥ 3 allergic reaction to treatment with a monoclonal antibody or has a known or suspected hypersensitivity to components of the study treatment(s).
• Baseline QT interval corrected by Fridericia's formula (QTcF) \> 480 milliseconds or known to have congenital prolonged QT syndrome.
• History of Grade ≥ 3 immune-related AEs (irAEs). Exceptions: hypothyroidism, type 1 diabetes mellitus (Type 1 DM), and dermatologic irAEs (patients with previous Steven Johnson Syndrome, toxic epidermal necrolysis or other severe forms of dermatitis are ineligible) are allowed. Type 1 DM should be controlled with HbA1c \<8% as per ADA recommendation.
• Receiving an immunologically based treatment for any reason, including chronic use of systemic steroids equivalent to \> 10 mg/day of prednisone within 7 days of the first dose of study drug or at any time during study participation.
• Note: Use of inhaled or topical steroids or systemic corticosteroids equivalent to ≤ 10 mg/day prednisone equivalent is permitted as is short-term use of corticosteroids at doses equivalent to \> 10 mg/day of prednisone (e.g., pre-medication prior to contrast).
• Treatment with systemic immune-stimulatory agents (e.g., IL-2, IFNγ) within 4 weeks prior to the first dose of study drug.
• History or current active or chronic autoimmune disease including but not limited to inflammatory bowel disease, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease.
• (Exception: Patients with vitiligo or resolved childhood asthma/atopy, hypothyroidism on stable hormone replacement, controlled asthma, Type I diabetes, Graves' disease, Hashimoto's disease, or with Medical Monitor approval)
• Clinically significant cardiac condition, including unstable angina, acute myocardial infarction within 6 months of Cycle 1 Day 1, New York Heart Association Class III or IV congestive heart failure, unstable angina pectoris or arrhythmia requiring therapy.

Sponsors & Collaborators

• Lyvgen Biopharma Holdings Limited: lead

Study Sites (1)

Center Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

MeSH Terms

Conditions

Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: December 9, 2021
• Study Start: September 29, 2021
• Primary Completion: December 19, 2023
• Study Completion: December 19, 2023
• Last Updated: April 22, 2024

Record last verified: 2024-04

Locations

CN (1)