SNV1521 for Advanced Cancer

Recruiting at 8 trial locations

Overseen By Robert Casper

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Synnovation Therapeutics, Inc.

Disqualifiers: Brain metastasis, Other malignancy, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is testing a new medicine, SNV1521, for people with advanced cancers. The researchers want to find out if SNV1521 is safe, well-tolerated, and effective in treating solid tumors. They are investigating different doses in order to find the most effective and safe one. They are also investigating whether it can be combined with other cancer therapies.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What safety data exists for SNV1521 (also known as VP-16-213) in humans?

VP-16-213 has been tested in various cancers, showing some side effects like leukopenia (low white blood cell count), nausea, vomiting, and hair loss, which were generally mild or reversible. In children with leukemia, it caused pancytopenia (low blood cell counts) and vomiting. Overall, it has been used safely in different cancer treatments with manageable side effects. ^{1 2 3 4 5}

What makes the drug SNV1521 unique for treating advanced cancer?

SNV1521 is unique because it targets CD151, a protein involved in cancer cell communication and metastasis (spread of cancer). By interfering with CD151, SNV1521 may reduce cancer cell invasion and growth, offering a novel approach compared to existing treatments. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for people with advanced solid tumors that are measurable, who have tried other treatments without success or can't tolerate them. Participants should be relatively active and mobile (ECOG status 0 or 1) and expected to live more than three months.

Inclusion Criteria

Life expectancy > 3 months

Evaluable or Measurable disease (RECIST 1.1 Criteria)

My cancer has spread beyond its original location.

Exclusion Criteria

I have a serious stomach or intestine condition.

I have liver problems.

I have active cancer spread to my brain or its coverings.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of SNV1521 to determine the maximum tolerated dose

28 days

Dose Expansion

Participants receive SNV1521 at the determined dose to evaluate safety and efficacy in specific cancer types

Up to 13 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• SNV1521

Trial Overview The study is testing SNV1521, a new medication for advanced cancers. It aims to determine the safety, tolerability, and effectiveness of SNV1521 by exploring different doses to find the best balance between efficacy and safety.

Participant Groups

Group I: Dose Expansion for Solid Tumors with Brain Metastases Experimental Treatment 1 Intervention

Group II: Dose Expansion for Pancreatic Ductal Adenocarcinoma Experimental Treatment 1 Intervention

Group III: Dose Expansion for Metastatic Castration Resistant Prostate Cancer Experimental Treatment 1 Intervention

Group IV: Dose Expansion Experimental Treatment 1 Intervention

Group V: Dose Escalation Experimental Treatment 1 Intervention

Group VI: Combination Dose Escalation Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Synnovation Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

340+

Findings from Research

In a phase II clinical trial involving 71 patients with lung cancer, VP-16-213 showed a 33.3% partial response rate in patients with small cell carcinoma, indicating its potential efficacy for this type of cancer.

The treatment was associated with manageable side effects, primarily leukopenia, nausea, vomiting, anorexia, and alopecia, suggesting that while it is effective, careful monitoring and possible dose adjustments may be necessary in future combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase II study of intravenous VP-16-213 in small cell and non-small cell carcinoma of the lung]. Konno, K., Nagahama, F., Nakai, Y., et al.[2013]

In a post-marketing survey of 4,177 patients with advanced gastric cancer, S-1 demonstrated a safety profile consistent with earlier studies, with 74% experiencing adverse events and 25% experiencing grade 3 or worse events.

The median survival time for patients treated with S-1 was 8.3 months, with a 1-year survival rate of 33.3%, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Japanese nationwide post-marketing survey of S-1 in patients with advanced gastric cancer]. Ohtsu, A.[2013]

In a study involving 10 children with various types of leukemia and histiocytic medullary reticulosis, VP 16-213 combined with other drugs showed effectiveness, particularly in acute non-lymphocytic leukemia, where one patient achieved complete response after treatment adjustments.

The treatment regimen caused significant side effects, including severe pancytopenia and vomiting, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[VP 16-213 in the treatment of acute leukemia in childhood]. Esumi, N., Arakawa, S., Imashuku, S.[2013]

In a late phase II clinical study involving 81 patients with advanced or refractory breast cancer, S-1 demonstrated a response rate of 42.0%, with a median survival period of 910 days, indicating its potential effectiveness as a treatment.

S-1 was associated with manageable adverse reactions, with severe side effects occurring in a small percentage of patients, suggesting it has a favorable safety profile compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A late phase II clinical study of S-1 in patients with progressed, refractory breast cancer]. Saeki, T., Takashima, S., Sano, M., et al.[2013]

In a study of 29 heavily pretreated non-Hodgkin lymphoma (NHL) patients, oral VP 16 showed significant activity with a combined complete response (CR) and partial response (PR) rate of 31%, with responses lasting up to 185 weeks.

For small cell lung cancer (SCLC), a combination treatment of VP 16 with other drugs resulted in a high CR rate of 90% in patients with limited disease and a median survival time exceeding one year for those who achieved CR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[VP 16-213]. Ogawa, M.[2013]

CD151 is a crucial protein that plays multiple roles in cancer progression, including supporting tumor growth and metastasis, making it a significant target for cancer therapies.

Reducing the interaction of CD151 with integrins can decrease cancer cell invasion and metastasis, suggesting that targeting CD151 could be an effective strategy in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD151-A Striking Marker for Cancer Therapy. Kumari, S., Devi, G., Badana, A., et al.[2020]

In a study using the MMTV-Wnt1 mouse model, the removal of CD151 alleles significantly reduced tumor-free survival from an average of 34 weeks to 22 and 18 weeks, indicating that CD151 plays a crucial role in suppressing tumor growth in breast cancer.

CD151 deficiency led to hyperactivation of the Wnt pathway and changes in cell characteristics, such as increased proliferation and decreased expression of myoepithelial markers, suggesting that CD151 helps counteract processes like epithelial-mesenchymal transition (EMT) that promote cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling. Li, H., Li, J., Han, R., et al.[2020]

CD151 plays a crucial role in breast cancer progression by regulating the interaction between ErbB2 and ErbB3, which affects how cancer cells respond to Herceptin (trastuzumab).

In clinical studies, CD151 was associated with improved overall and progression-free survival in patients with ErbB2-overexpressing tumors that were ErbB3-negative, highlighting its potential as a biomarker for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetraspanin CD151 impairs heterodimerization of ErbB2/ErbB3 in breast cancer cells. Mieszkowska, M., Piasecka, D., Potemski, P., et al.[2019]

Knocking down the CD151 gene in breast cancer cell lines (MCF-7 and MDA-MB-468) significantly reduces their ability to proliferate, migrate, and invade, indicating that CD151 plays a crucial role in promoting aggressive cancer behaviors.

The study suggests that targeting CD151 could be a promising therapeutic strategy for treating luminal and basal-like breast cancer subtypes, as its silencing leads to increased apoptosis and cell cycle arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD151 by lentivirus-mediated RNA interference inhibits luminal and basal-like breast cancer cell growth and invasion. Liu, T., wang, S., Wang, L., et al.[2018]

In a study of 179 colorectal cancer patients, high CD151 expression was found in 48% of early-stage cases, but only 33% in those with metastatic colon cancer, suggesting that CD151 may play a role in the progression of the disease.

The research indicates that as tumor invasion and metastatic stages increase, CD151 expression decreases, highlighting its potential as a biomarker for assessing cancer progression in colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic change of tetraspanin CD151 membrane protein expression in colorectal cancer patients. Lin, PC., Lin, SC., Lee, CT., et al.[2017]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[A phase II study of intravenous VP-16-213 in small cell and non-small cell carcinoma of the lung]. [2013]

2. Japan pubmed.ncbi.nlm.nih.gov

[Japanese nationwide post-marketing survey of S-1 in patients with advanced gastric cancer]. [2013]

3. Japan pubmed.ncbi.nlm.nih.gov

[VP 16-213 in the treatment of acute leukemia in childhood]. [2013]

4. Japan pubmed.ncbi.nlm.nih.gov

[A late phase II clinical study of S-1 in patients with progressed, refractory breast cancer]. [2013]

5. Japan pubmed.ncbi.nlm.nih.gov

[VP 16-213]. [2013]

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

CD151-A Striking Marker for Cancer Therapy. [2020]

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

Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling. [2020]

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

Tetraspanin CD151 impairs heterodimerization of ErbB2/ErbB3 in breast cancer cells. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting CD151 by lentivirus-mediated RNA interference inhibits luminal and basal-like breast cancer cell growth and invasion. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Dynamic change of tetraspanin CD151 membrane protein expression in colorectal cancer patients. [2017]