SNV4818 for Cancer

Recruiting at 7 trial locations

Overseen By Robert Casper

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Synnovation Therapeutics, Inc.

Disqualifiers: CNS malignancy, Brain metastases, Diabetes, others

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

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

140 Participants Needed

Trial Summary

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

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What safety data exists for SNV4818 or similar treatments?

The research articles do not provide specific safety data for SNV4818, but they discuss cardiovascular risks associated with similar cancer treatments, like tyrosine kinase inhibitors, which can cause heart-related side effects such as heart failure and blood clots. ^{1 2 3 4 5}

What is the purpose of this trial?

This study is testing a new medicine, SNV4818, for people with advanced cancers. The researchers want to find out if SNV4818 is safe, well-tolerated, and effective in treating solid tumors. They are investigating different doses in order to find the safest and most effective one.

Eligibility Criteria

This trial is for individuals with advanced solid tumors. Participants must have a type of cancer that has progressed despite treatment, or for which no standard treatment exists.

Inclusion Criteria

My cancer can be measured by scans or blood tests.

My condition hasn't improved with current treatments or they cause me severe side effects.

My cancer has a PIK3CA mutation.

Exclusion Criteria

Clinically significant ECG abnormalities, including QTcF ≥ 470 ms

I have type 1 diabetes or my type 2 diabetes is not under control.

My organs are not functioning properly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral, daily doses of SNV4818 as monotherapy or in combination with Fulvestrant, with dose escalation and expansion cohorts

8 weeks

Weekly visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are monitored for duration of response and disease progression

Up to approximately 2 years

Treatment Details

Interventions

• SNV4818

Trial Overview The study is evaluating the safety and effectiveness of a new medication called SNV4818, in various doses, to treat advanced cancers. It's also comparing SNV4818's effects when used alone versus combined with Fulvestrant.

Participant Groups

Group I: SNV4818+Fulvestrant Combination Experimental Treatment 2 Interventions

Participants will receive oral, daily doses of SNV4818 in combination with a standard dose of Fulvestrant as part of either dose escalation or dose expansion cohorts.. The SNV4818 dose level participants receive will depend upon the study part to which they are assigned. Dose escalation participants will be assigned to small cohorts of ascending SNV4818 dose levels. Dose expansion participants will receive one of the SNV4818 dose levels recommended for further evaluation.

Group II: SNV4818 Monotherapy Experimental Treatment 1 Intervention

Participants will receive oral, daily doses of SNV4818 as a single agent as part of either dose escalation or dose expansion cohorts. The SNV4818 dose level participants receive will depend upon the study part to which they are assigned. Dose escalation participants will be assigned to small cohorts of ascending SNV4818 dose levels. Dose expansion participants will receive one of the SNV4818 dose levels recommended for further evaluation.

Who Is Running the Clinical Trial?

Synnovation Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

340+

Pikavation Therapeutics, Inc.

Lead Sponsor

Findings from Research

In a study of 988 patients with metastatic renal cell carcinoma, over 65% of those new to VEGFR-TKIs experienced anti-angiogenesis-related adverse events, with hypertension being the most common side effect.

Patients who experienced these adverse events were 1.6 times more likely to receive a lower dose intensity of their VEGFR-TKI treatment, indicating that side effects can impact the effectiveness of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Anti-Angiogenesis-Related Adverse Events Associated with Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors (VEGFR-TKIs) in Patients with Metastatic Renal Cell Carcinoma. Lee, N., Lee, JL., Lee, JY.[2023]

Ponatinib, a treatment for chronic myelogenous leukemia patients with the T315I mutation, has been identified as the most cardiotoxic tyrosine kinase inhibitor, with a mechanism involving excessive cardiac inflammation.

The study revealed that ponatinib activates the S100A8/A9-TLR4-NLRP3-IL-1β signaling pathway, leading to cardiac dysfunction, and suggests that immunosuppressive treatments like dexamethasone could help manage this cardiotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation. Tousif, S., Singh, AP., Umbarkar, P., et al.[2023]

In a retrospective analysis of seven patients with Philadelphia chromosome-positive leukemia treated with ponatinib, significant vascular adverse events (VAEs) such as cerebral infarction and unstable angina were observed, highlighting the need for careful monitoring despite prophylactic aspirin use.

Patients with pre-existing risk factors or a history of lifestyle diseases, especially those on long-term second tyrosine kinase inhibitor treatment, are at increased risk for VAEs and require targeted monitoring and intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vascular adverse events of ponatinib during treatment of Philadelphia chromosome-positive leukemia: a retrospective single-institution analysis]. Sato, N., Yuda, J., Yamauchi, N., et al.[2020]

Molecular targeted therapies, such as monoclonal antibodies and tyrosine kinase inhibitors, can cause significant cardiovascular side effects, including heart failure and dysrhythmias, highlighting the need for careful monitoring.

There is a call for a multidisciplinary approach involving cardio-oncologists and other healthcare professionals to manage and monitor these cardiovascular risks effectively, emphasizing the importance of onco-vigilance in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular toxicity of anticancer-targeted therapy: emerging issues in the era of cardio-oncology. Raschi, E., De Ponti, F.[2022]

In a study of 53 patients with advanced cancer, regorafenib showed minimal impact on the QTc interval, with no significant changes that would raise clinical concerns, indicating a favorable cardiovascular safety profile.

The mean change in left ventricular ejection fraction (LVEF) was also modest, suggesting that regorafenib does not significantly affect heart function, which is important for patients undergoing cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I open-label trial evaluating the cardiovascular safety of regorafenib in patients with advanced cancer. Jones, RL., Bendell, JC., Smith, DC., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

Analysis of Anti-Angiogenesis-Related Adverse Events Associated with Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors (VEGFR-TKIs) in Patients with Metastatic Renal Cell Carcinoma. [2023]

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

Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation. [2023]

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

[Vascular adverse events of ponatinib during treatment of Philadelphia chromosome-positive leukemia: a retrospective single-institution analysis]. [2020]

4. Italy pubmed.ncbi.nlm.nih.gov

Cardiovascular toxicity of anticancer-targeted therapy: emerging issues in the era of cardio-oncology. [2022]

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

A phase I open-label trial evaluating the cardiovascular safety of regorafenib in patients with advanced cancer. [2022]