LVGN3616 + LVGN6051 Combinations for Advanced Cancers

Overseen By Siqing Fu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiepileptics, Steroids, HAART, others

Disqualifiers: Infections, Heart failure, Hypertension, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests combinations of new treatments for advanced cancers to determine their ability to stop or shrink tumors. It targets cancers that are advanced, recurrent, unresponsive to other treatments, or have metastasized. Participants should have a type of solid tumor that standard treatments can't effectively address and must have a specific molecular profile confirmed by a lab test. The trial includes LVGN3616 (also known as Nivolumab or Opdivo) and LVGN6051 as part of the treatment combinations. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive potentially groundbreaking therapies.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that certain treatments for systemic tumor control should not be given within specific time frames before starting the trial. It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the drug used in Regimen A, nanoparticle albumin-bound paclitaxel, is generally well tolerated and safer than its traditional form. In Regimen B, the drugs bevacizumab and cyclophosphamide are commonly used in cancer treatments and have well-known safety records. The FDA has approved bevacizumab for certain cancers, indicating its safety. Cyclophosphamide is a standard chemotherapy drug with known side effects.

For Regimen C, early studies suggest that LVGN7409 is reasonably safe for patients with advanced cancers. Previous research also considers its combination with nab-paclitaxel safe. In Regimen D, the combination includes drugs like bevacizumab and cyclophosphamide, which have established safety records, along with new drugs that have shown promising early safety results.

Since this trial is in phase 1, it mainly focuses on safety and dosage, leaving much to learn about the treatments' safety. However, using drugs with known safety records and early positive safety data from new drugs offers some reassurance about safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore innovative combinations of drugs for advanced cancers, potentially offering new hope where standard treatments like chemotherapy, radiation, and targeted therapies may have fallen short. LVGN3616 and LVGN6051, at the core of all trial regimens, are designed to work together to enhance the immune system's ability to fight cancer, which is different from traditional options primarily aimed at killing cancer cells directly. Additionally, the inclusion of novel agents like LVGN7409 and the strategic use of known drugs such as Bevacizumab, Nab-Paclitaxel, and Cyclophosphamide in these novel combinations could lead to more effective treatment strategies for cancers that are hard to treat or have spread. This approach is hoped to offer more effective options for patients with advanced, relapsed, or refractory cancers.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research has shown that nab-paclitaxel, part of the Regimen A: LVGN3616 + LVGN6051 + Nab-Paclitaxel treatment plan in this trial, effectively treats several adult cancers, including breast cancer. Bevacizumab, included in Regimen B: LVGN3616 + LVGN6051 + Bevacizumab + Cyclophosphamide, stops the growth of blood vessels that supply tumors, which can slow cancer growth. Cyclophosphamide, also part of this regimen, is a chemotherapy drug that kills cancer cells by damaging their DNA. The LVGN7409 component, used in both Regimen C: LVGN3616 + LVGN6051 + LVGN7409 + Nab-Paclitaxel and Regimen D: LVGN3616 + LVGN6051 + LVGN7409 + Bevacizumab + Cyclophosphamide, boosts the immune system's ability to fight cancer. Together, these treatments aim to attack cancer from different angles, increasing their potential effectiveness in advanced cancers. ^{2 5 6 7 8}

Who Is on the Research Team?

Siqing FU, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults (≥18 years) with certain metastatic solid tumors, measurable disease, good performance status (ECOG 0-1), and adequate organ function can join. They must not have unresolved significant side effects from past treatments or be on conflicting trials or medications. Pregnant women, those with active severe infections like HIV/Hepatitis B/C, recent live vaccines, autoimmune diseases needing treatment in the last 2 years, or a history of severe reactions to monoclonal antibody therapy are excluded.

Inclusion Criteria

I finished any palliative radiation at least a week ago.

I have had treatments like immunotherapy or chemotherapy, but not with specific drugs targeting PD1/PD-L1 along with CD137 or CD40.

My cancer has spread, lacks standard treatment options, and has been tested in a certified lab.

Exclusion Criteria

Lactation or pregnancy

You have had an allergic reaction to the study drugs in the past.

I am on HAART for HIV or have active hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LVGN3616 and LVGN6051 ± LVGN7409 in combination with nab-paclitaxel or bevacizumab and cyclophosphamide to determine the maximum tolerated dose and evaluate antitumor activity

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Cyclophosphamide
• LVGN3616
• LVGN6051
• LVGN7409
• Nab-Paclitaxel

Trial Overview The trial is testing combinations of new drugs LVGN3616 and LVGN6051 with/without LVGN7409 alongside Nab-Paclitaxel or Bevacizumab and Cyclophosphamide for their effectiveness against selected metastatic cancers. It's an early-phase study to see how well these drug combos work.

How Is the Trial Designed?

Group I: Regimen D: LVGN3616 + LVGN6051 + LVGN7409 + Bevacizumab + Cyclophosphamide Experimental Treatment 4 Interventions

given in combination with other drugs to patients with cancers that are advanced, relapsed (have come back), refractory (have not responded to treatment), or metastatic (have spread).

Group II: Regimen C: LVGN3616 + LVGN6051 + LVGN7409 + Nab-Paclitaxel Experimental Treatment 4 Interventions

given in combination with other drugs to patients with cancers that are advanced, relapsed (have come back), refractory (have not responded to treatment), or metastatic (have spread).

Group III: Regimen B: LVGN3616 + LVGN6051 + Bevacizumab + Cyclophosphamide Experimental Treatment 4 Interventions

given in combination with other drugs to patients with cancers that are advanced, relapsed (have come back), refractory (have not responded to treatment), or metastatic (have spread).

Group IV: Regimen A: LVGN3616 + LVGN6051 + Nab-Paclitaxel Experimental Treatment 4 Interventions

given in combination with other drugs to patients with cancers that are advanced, relapsed (have come back), refractory (have not responded to treatment), or metastatic (have spread).

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Lyvgen Biopharma Holdings Limited

Industry Sponsor

Trials

7

Recruited

930+

Published Research Related to This Trial

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

Citations

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LVGN3616 + LVGN6051 Combinations for Advanced ... This trial is testing new cancer drugs combined with existing chemotherapy treatments. It targets patients with specific types of tumors that may not ...

2. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2021-0176.html

Phase I Study of LVGN3616 plus LVGN6051 and/or ... This is an investigator-initiated industry-supported phase 1 clinical trial conducted in the phase 1 clinic at The University of Texas MD Anderson Cancer ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-10729

LVGN3616 and LVGN6051 and/or LVGN7409 in ... This phase I trial tests the safety, side effects, and best dose of LVGN3616, LVGN6051, and LVGN7409 in combination with nab-paclitaxel (or equivalent ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12295115/

Advances and Challenges in Immunotherapy for Metastatic ... Spartalizumab and LVGN3616 are monoclonal antibodies (mAbs) targeting the PD-1 receptor, designed to restore T cell-mediated anti-tumor activity ...

5. lyvgen.com lyvgen.com/lvgn7409

LVGN7409 - Lyvgen Biopharma Website 礼进生物 英文官网 VIEW TRIAL. Study of LVGN3616 and LVGN6051±LVGN7409 in Combination With Nab-Paclitaxel or Bevacizumab and Cyclophosphamide in Metastatic Solid Tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05075993

Study of LVGN3616 and LVGN6051±LVGN7409 in ... Regimen A: LVGN3616 + LVGN6051 + Nab-Paclitaxel. given in combination with other drugs to patients with cancers that are advanced, relapsed (have come back) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12037671/

The Efficacy and Safety of Nivolumab Combined with Nab ... Our study suggested that nivolumab combined with chemotherapy was effective and safe as a first-line intervention for advanced gastric cancer.

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05075993/study-of-lvgn3616-and-lvgn6051lvgn7409-in-combination-with-nab-paclitaxel-or-bevacizumab-and-cyclophosphamide-in-metastatic-solid-tumors

Study of LVGN3616 and LVGN6051±LVGN7409 in ... Study of LVGN3616 and LVGN6051±LVGN7409 in Combination With Nab-Paclitaxel or Bevacizumab and Cyclophosphamide in Metastatic Solid Tumors.