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

352 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing new cancer drugs combined with existing chemotherapy treatments. It targets patients with specific types of tumors that may not respond well to standard treatments. The new drugs aim to stop cancer cells from growing or make them more vulnerable to chemotherapy.

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.

What data supports the effectiveness of the drug nanoparticle albumin-bound paclitaxel (Abraxane) in treating advanced cancers?

Research shows that nanoparticle albumin-bound paclitaxel (Abraxane) is effective in treating several adult cancers, including breast cancer, where it has been associated with a better response rate and longer survival compared to conventional treatments. ^{1 2 3 4 5}

Is the treatment of LVGN3616 + LVGN6051 combinations for advanced cancers generally safe in humans?

Nanoparticle albumin-bound paclitaxel (Abraxane) is generally well tolerated and associated with a safer administration compared to conventional paclitaxel, as it avoids the use of a toxic solvent. It has been shown to be well tolerated in patients with breast cancer and non-small-cell lung cancer. ^{1 2 5 6 7}

What makes the drug combination of LVGN3616, LVGN6051, and others unique for advanced cancers?

This drug combination is unique because it includes nanoparticle albumin-bound paclitaxel (Abraxane), which allows for safer administration without toxic solvents, potentially leading to higher drug concentration in tumors and improved outcomes compared to conventional paclitaxel. ^{1 2 3 5 6}

Research Team

Siqing FU, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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 am 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. United States 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). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Is nab-paclitaxel better than conventional taxanes as neoadjuvant therapy for breast cancer? A meta-analysis. [2021]

3. China pubmed.ncbi.nlm.nih.gov

[Efficacy of albumin-bound paclitaxel in advanced gastric cancer patients]. [2018]

4. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with conventional taxanes in women with breast cancer: a systematic review and meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. [2023]

6. France 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. [2022]

7. England 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. [2022]