LVGN6051 + Pembrolizumab for Metastatic Cancer

Not currently recruiting at 6 trial locations

Overseen By Lynn Jiang, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Lyvgen Biopharma Holdings Limited

Must not be taking: Immunotherapy, Immune-stimulatory agents

Disqualifiers: CNS metastasis, 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 explores a new treatment for individuals with advanced or metastatic cancer that has spread. The focus is on testing LVGN6051, a drug targeting cancer cells, either alone or with Pembrolizumab (an immunotherapy). Researchers aim to determine the best and safest dose of this treatment. Suitable candidates for this trial include those diagnosed with metastatic or advanced cancer that surgery cannot remove. 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 this new therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot have had recent systemic anticancer therapy or certain immune treatments. It's best to discuss your specific medications with the trial team.

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

Research has shown that LVGN6051, when used alone, is generally well-tolerated by patients. In some studies, seven out of ten patients experienced stable disease, meaning their cancer did not worsen over time. This suggests the treatment might be safe for people with advanced or spreading cancer.

When combined with Pembrolizumab, a medication already used to treat certain cancers like melanoma and lung cancer, LVGN6051 has also been well-tolerated. Researchers have identified doses that patients can handle without serious side effects. This combination is currently being tested for effectiveness.

Overall, early studies suggest that both LVGN6051 alone and with Pembrolizumab have been safe for patients so far. However, more research is needed to confirm these findings and to learn more about possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

LVGN6051 is unique because it represents a novel approach in the treatment of metastatic cancer by targeting the CD137 receptor, an immune checkpoint that can enhance the body’s immune response against tumors. Unlike traditional treatments that often involve chemotherapy or standard immunotherapy, LVGN6051 is designed to be administered through an intravenous infusion every three weeks, potentially improving patient convenience and adherence. Researchers are excited about this treatment because it could offer a more targeted attack on cancer cells, possibly leading to more effective and personalized cancer care.

What evidence suggests that LVGN6051 might be an effective treatment for metastatic cancer?

Research has shown that LVGN6051, a specially designed antibody, produced promising results in earlier studies by shrinking tumors in patients unresponsive to previous treatments known as immune checkpoint inhibitors (ICIs). In this trial, participants will receive LVGN6051, with some also receiving pembrolizumab, another cancer treatment. Patients have tolerated the combination of LVGN6051 and pembrolizumab well. This combination has shown potential in slowing the progression of advanced or spreading cancers. These early findings suggest that LVGN6051 could be a helpful option for patients with difficult-to-treat cancers. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic cancer who have a life expectancy of at least 90 days and are in good organ function. They must not be on immunotherapy, have active autoimmune diseases, severe heart conditions, recent infections requiring IV drugs, lung disease needing steroids, or be pregnant/breastfeeding. HIV-positive patients can join if well-controlled.

Inclusion Criteria

I agree to use highly effective birth control methods.

My HIV is under control with effective treatment.

My bone marrow, liver, and kidneys are functioning well.

Exclusion Criteria

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

I've had a severe allergic reaction to a monoclonal antibody treatment.

My cancer has spread to my brain or the membranes around my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of LVGN6051 to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) and recommended Phase 2 dose(s) (RP2D)

up to 24 months

Every 3 weeks (Q3W) for up to 35 cycles

Dose Expansion

Participants receive the recommended dose of LVGN6051 in combination with pembrolizumab to further evaluate safety and efficacy

up to 24 months

Every 3 weeks (Q3W) for up to 35 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LVGN6051

Trial Overview The trial is testing LVGN6051 alone and combined with Pembrolizumab 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 people with advanced cancers.

How Is the Trial Designed?

Group I: LVGN6051 Experimental Treatment 2 Interventions

The dose escalation phase includes 10 dose levels of LVGN6051, and the highest dose is up to 10mg/kg. 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+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed an overall objective response rate of 33%, indicating its efficacy in treating this type of cancer.

The median overall survival for patients receiving pembrolizumab was 23 months, with a 12-month survival rate of 66%, while 14% of patients experienced severe treatment-related adverse events, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. Ribas, A., Hamid, O., Daud, A., et al.[2022]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

A study of 112 patients with non-small cell lung cancer (NSCLC) found that EBUS TBNA is effective for obtaining samples suitable for PD-L1 testing, with 82% of samples adequate for all ancillary tests.

The results showed a high satisfaction rate for PD-L1 expression testing, with 86% of cases yielding satisfactory results and 32% of patients exhibiting high PD-L1 expression levels (>50%), which is important for treatment decisions with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. Biswas, A., Leon, ME., Drew, P., et al.[2018]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

In a phase 2 trial involving 12 patients with advanced osteosarcoma, pembrolizumab showed no clinical benefit at 18 weeks, with all patients experiencing disease progression and a median overall survival of only 6.6 months.

Despite the lack of significant antitumor activity, pembrolizumab was well-tolerated, with no treatment-related deaths or severe adverse events, suggesting it may be safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Boye, K., Longhi, A., Guren, T., et al.[2022]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2525

First-in-human, phase 1a dose finding of LVGN6051 ... Preliminary efficacy data showed encouraging anti-tumor activity in heavily pretreated pts who had progressed on ICI. Phase 1b dose ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.2521

Early safety and efficacy from a phase I open-label clinical ... Conclusions: Preliminary evidence showed that LVGN6051 was well tolerated and tumor shrinkages were observed. While we continue assessing its ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06378177?term=LVGN6051&rank=3

A Study of LVGN6051 Combination Therapy in Patient With ... The purpose of this study is to assess the safety and efficacy of LVGN6051 (4-1BB agonistic antibody) combined with toripalimab (anti-PD-1 antibody) and ...

4. withpower.com withpower.com/trial/lvgn6051-pembrolizumab-for-metastatic-cancer-ed90c

LVGN6051 + Pembrolizumab for Metastatic Cancer A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05301764

A Study of LVGN6051 Combined with Anlotinib in Patient ... To assess the preliminary efficacy of LVGN6051 combined with Anlotinib in terms of disease control rate (DCR), Up to 24 months. To assess whether the anti ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT404420

First-in-human, phase 1a dose finding of LVGN6051 ... Conclusions: We established the RP2Ds of LVGN6051 alone and in combination with pembrolizumab in this FIH phase 1a study. These regimens were well tolerated.

7. ctv.veeva.com ctv.veeva.com/study/study-of-lvgn6051-cd137-agonist-antibody-in-advanced-or-metastatic-malignancy

Study of LVGN6051 (CD137 Agonist Antibody) in Advanced or ... The study of LVGN6051-201 is designed to use a bridging dose escalation to quickly establish the maximum tolerated dose (MTD) and/or the ...