LVGN7409 for Advanced or Metastatic Cancer

Overseen By Lynn Jiang, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Lyvgen Biopharma Holdings Limited

Must not be taking: Immunotherapy, Live-virus vaccines

Disqualifiers: Autoimmune disease, Cardiac condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LVGN7409 (a CD40 agonist), designed for people with advanced or metastatic cancer. Researchers aim to determine the best dose of this treatment, both alone and in combination with other cancer drugs. The trial seeks participants diagnosed with cancer that has spread or cannot be surgically removed, and who are expected to live at least another three months. The goal is to assess the effectiveness and safety of this new treatment for future use in similar patients. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are receiving an immunologically based treatment, you may not be eligible to participate.

Is there any evidence suggesting that LVGN7409 is likely to be safe for humans?

Research has shown that LVGN7409, a new treatment under study, demonstrated promising safety results in early tests. In previous studies, LVGN7409 had a better safety profile compared to similar treatments, causing fewer side effects.

LVGN7409 targets a protein called CD40, which aids the immune system in fighting cancer cells. Although treatments like this can sometimes cause side effects, LVGN7409 was designed to minimize these issues.

As a new treatment, it is being tested in a first-in-human study. This study focuses on finding the best and safest dose for people. Researchers are closely monitoring for any side effects to ensure the treatment's safety for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

LVGN7409 is unique because it offers a novel approach for treating advanced or metastatic cancer. Unlike traditional chemotherapy that targets all rapidly dividing cells, LVGN7409 is designed to specifically target cancer cells, potentially reducing side effects. Administered via IV infusion once every three weeks, it introduces a new dosing schedule that could improve patient convenience. Researchers are excited because this targeted mechanism might lead to more effective treatments with fewer adverse effects, offering hope for better outcomes.

What evidence suggests that LVGN7409 might be an effective treatment for advanced or metastatic cancer?

Research has shown that LVGN7409, a specially designed antibody, may help treat advanced cancers. Lab tests demonstrated that LVGN7409 had stronger effects against tumors and was safer compared to similar treatments. In early studies, some patients experienced tumor shrinkage, and a few achieved complete recoveries in cases of melanoma and breast cancer. However, initial trials with similar treatments often showed low success rates when used alone. These results are promising, but further research is needed to confirm its effectiveness in people.

Participants in this trial will receive LVGN7409 as a monotherapy, with dose escalation to determine the optimal dose. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic cancer who have recovered from previous treatments, have good organ function, and are not pregnant can join. They must agree to use effective birth control. People with heart issues, severe immune-related side effects from past therapies, recent strokes, organ transplants, live vaccines within a month, ongoing immunotherapy for other conditions or specific allergies cannot participate.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document.

My blood, liver, and kidney tests are within normal ranges.

I have HIV but it is well-managed with medication.

Exclusion Criteria

I have not received a live-virus vaccine in the last 30 days.

I do not have uncontrolled fluid buildup in my chest, heart, or abdomen.

I have an autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive LVGN7409 as monotherapy in an accelerated dose escalation to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)

up to 24 months

Every 3 weeks (Q3W)

Dose Expansion

Participants receive LVGN7409 in combination with anti-PD-1 antibody and/or CD137 agonist to further evaluate safety and efficacy

up to 24 months

Every 3 weeks (Q3W)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LVGN7409

Trial Overview The trial is testing LVGN7409 alone and in combination with an anti-PD-1 antibody and/or CD137 agonist to find the safest dose for future studies. It aims to determine how much of these drugs can be given without causing serious side effects in patients with advanced cancers.

How Is the Trial Designed?

Group I: Monotherapy dose escalation Experimental Treatment 1 Intervention

The monotherapy dose escalation phase includes 8 dose levels of LVGN7409. 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.

Who Is Running the Clinical Trial?

Lyvgen Biopharma Holdings Limited

Lead Sponsor

Trials

7

Recruited

930+

Published Research Related to This Trial

Agonistic CD40 monoclonal antibodies (mAb) have shown promise in activating the immune system to generate anticancer responses, potentially offering a new therapeutic option that works differently from traditional immune checkpoint inhibitors like anti-CTLA-4 or anti-PD-1.

Initial clinical trials indicate that agonistic CD40 mAb can produce effective antitumor responses without significant toxicity, suggesting a safe profile for use in cancer treatment, although further research is needed to optimize dosing and administration strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agonistic CD40 antibodies and cancer therapy. Vonderheide, RH., Glennie, MJ.[2022]

CD40 agonists have shown potential in cancer immunotherapy, demonstrating moderate antitumor effects in some tumors, based on early clinical trials.

The adverse events associated with CD40 agonists, such as cytokine release and hepatotoxicity, have been mostly transient and manageable, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and clinical trial results of agonistic anti-CD40 antibodies in the treatment of malignancies. Li, DK., Wang, W.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04635995

Phase 1 Trial of LVGN7409 (CD40 Agonist Antibody) as ... This first in human study of LVGN7409 is designed to establish the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE) as well as the ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e14501

Early safety and efficacy from a phase I open-label clinical ... LVGN7409 demonstrated more robust antitumor efficacy and superior safety profile than published CD40 agonist antibodies in preclinical models.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6169575/

Long-term outcomes of a phase I study of agonist CD40 ... With a median follow-up of 45 months, the median progression-free survival (PFS) was 3.2 months (95% CI, 1.3–5.1 months) and median overall ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1535610825003198

Fc-optimized CD40 agonistic antibody elicits tertiary ... Six patients experienced tumor reduction, including two complete responses in melanoma and breast cancer. 2141-V11 induced regression in ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/31/11/2079/762533/Facts-and-Hopes-of-CD40-Agonists-in-Cancer

Facts and Hopes of CD40 Agonists in Cancer Immunotherapy Initial clinical trials of CD40 agonists as monotherapy in patients with advanced solid tumors were safe but generally had low response rates.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e14501

Early safety and efficacy from a phase I open-label clinical ... LVGN7409 demonstrated more robust antitumor efficacy and superior safety profile than published CD40 agonist antibodies in preclinical models.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11177954/

Intratumoral Fc-optimized agonistic CD40 antibody induces ... Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer.

8. lyvgen.com lyvgen.com/7409fih

Lyvgen CD40 FIH LVGN7409 is xLinkAb anti-CD40 agonist mAb that has been designed to activate CD40 optimally in tumor microenvironment by targeting both CD40 and ...