VVD-130850 for Advanced Cancer

Recruiting at17 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Vividion Therapeutics, Inc.

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Cardiac diseases, CNS malignancies, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called VVD-130850 to see if it is safe and how it behaves in the body. The study focuses on patients with advanced solid and blood-related cancers. Researchers want to know if the drug can help fight cancer on its own and if it can make other immune-based treatments more effective.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or systematic steroid therapy, you may not be eligible to participate.

How is the drug VVD-130850 different from other cancer treatments?

VVD-130850, also known as VP-16-213 or etoposide, is unique because it targets cancer cells during specific phases of their growth cycle, making it effective in certain cancers like small-cell lung cancer and ovarian carcinoma. It can be administered both intravenously and orally, and is often used in combination with other drugs to enhance its effectiveness. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

This trial is for individuals with advanced solid tumors or blood cancers who have not responded to standard treatments. Participants must be adults, able to give consent, and meet specific health criteria.

Inclusion Criteria

My cancer is advanced and cannot be removed by surgery.

I am fully active or can carry out light work.

My organs and bone marrow are working well.

Exclusion Criteria

I have had a transplant from another person.

I am allergic to pembrolizumab or its ingredients.

I have an immune system disorder or am on medication that weakens my immune system.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ascending doses of VVD-130850, orally, once daily, with or without pembrolizumab IV infusion, in 21-day treatment cycles

21 days per cycle

1 visit every 3 weeks

Dose Expansion

Participants receive VVD-130850 at the recommended dose for expansion, orally, once daily, with or without pembrolizumab IV infusion, in 21-day treatment cycles

21 days per cycle

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 4 years

Treatment Details

Interventions

• Pembrolizumab (Checkpoint Inhibitor)
• VVD-130850 (Other)

Trial Overview The study tests VVD-130850 alone and combined with Pembrolizumab (a checkpoint inhibitor) to assess safety, how the body processes it, and its effects on cancer cells in patients with advanced tumors.

Participant Groups

Group I: Dose Expansion: VVD-130850 Single Agent Experimental Treatment 1 Intervention

Participants will receive VVD-130850 at recommended dose for expansion (RDE), orally, once daily in 21-day treatment cycles during the dose expansion phase.

Group II: Dose Expansion: VVD-130850 + Pembrolizumab Combination Therapy Experimental Treatment 2 Interventions

Participants will receive VVD-130850 at RDE orally, once daily along with pembrolizumab IV infusion, Q3W in 21-day treatment cycles during the dose expansion phase.

Group III: Dose Escalation: VVD-130850 Single Agent Experimental Treatment 1 Intervention

Participants will receive ascending doses of VVD-130850, orally, once daily in 21-day treatment cycles during the dose escalation phase.

Group IV: Dose Escalation: VVD-130850 + Pembrolizumab Combination Therapy Experimental Treatment 2 Interventions

Participants will receive ascending doses of VVD-130850, orally, once daily, along with pembrolizumab intravenous (IV) infusion, every 3 weeks (Q3W) in 21-day treatment cycles during the dose escalation phase.

Who Is Running the Clinical Trial?

Vividion Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

780+

Findings from Research

In a Phase II study involving 14 patients with advanced cervical carcinoma, the combination of VP-16 (etoposide), ifosfamide, and cisplatin (VIP) resulted in complete responses in 8 patients, with response durations lasting between 7 to over 24 months.

The VIP chemotherapy regimen was well-tolerated overall, with manageable hematologic toxicity being the primary side effect, indicating its potential as an effective treatment option for advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide (VP-16), ifosfamide/mesna, and cisplatin chemotherapy for advanced and recurrent carcinoma of the cervix. Kredentser, DC.[2019]

In a study of 25 patients with advanced ovarian carcinoma, VP-16-213 showed a 22% response rate, including one complete response, indicating its potential effectiveness even in patients previously treated with cis-platinum.

The treatment was well-tolerated with mild toxicity, and the median duration of response was 20 weeks, with a median survival of 32 weeks, suggesting that VP-16-213 warrants further investigation, particularly in combination with cis-platinum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of VP-16-213 in advanced ovarian carcinoma. Hillcoat, BL., Campbell, JJ., Pepperell, R., et al.[2019]

In a study of 27 patients with advanced breast cancer who were resistant to previous treatments, the combination of VP 16-213 and cyclophosphamide resulted in a 15% complete response rate and a 26% partial response rate, indicating its efficacy in difficult-to-treat cases.

Despite its effectiveness, the treatment was associated with significant side effects, including gastrointestinal toxicity in all patients and bone marrow toxicity in 81%, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VP16-213 and cyclophosphamide in advanced breast cancer. A phase II study. Estapé, J., Cirera, L., Millá, A., et al.[2019]

VP 16-213, a new semisynthetic epipodophyllotoxin, demonstrated clinically valuable antitumor activity in a phase II trial involving 33 patients with solid tumors and acute leukemias, particularly showing promising results in patients with oat cell carcinoma of the lung.

The drug was generally well tolerated, but it commonly caused side effects like leukothrombopenia and hair loss, indicating a need for further studies to optimize its dosage and explore its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. Jungi, WF., Senn, HJ., Beckmann, C., et al.[2013]

VM 26 and VP 16-213, epipodophyllotoxin derivatives entering phase III studies, show significant effectiveness against small-cell lung carcinoma and other cancers, particularly in the late S and G2 phases of the cell cycle.

VP 16-213 has demonstrated notable clinical activity in various cancers, including Hodgkin's disease and non-Hodgkin lymphomas, suggesting it may be prioritized over VM-26 for further development and research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The epipodophyllotoxin derivatives VM-26 and VP-16-213, 1976-1979, a review. Nissen, NI., Dombernowsky, P., Hansen, HH., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Etoposide (VP-16), ifosfamide/mesna, and cisplatin chemotherapy for advanced and recurrent carcinoma of the cervix. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of VP-16-213 in advanced ovarian carcinoma. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

VP16-213 and cyclophosphamide in advanced breast cancer. A phase II study. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

The epipodophyllotoxin derivatives VM-26 and VP-16-213, 1976-1979, a review. [2019]