SNV4818 for Cancer

Recruiting at 10 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine called SNV4818 for individuals with advanced cancers. Researchers aim to determine if SNV4818 is safe and effective for solid tumors. They are exploring different doses to identify the optimal one. Some participants will take SNV4818 alone, while others will combine it with another drug, Fulvestrant. The trial suits those with a specific gene mutation in their tumor (PIK3CA mutation) who have tried other treatments without success or experienced adverse side effects. As a Phase 1 trial, this research focuses on understanding how SNV4818 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that specific safety information for SNV4818 remains limited. This new treatment is being tested in patients with advanced cancers to assess its safety and tolerability. In these early studies, researchers are experimenting with different doses to identify the safest and most effective one.

While detailed safety data for SNV4818 is not yet available, it is important to note that the treatment targets a protein called PI3Kα, which has been linked to safety concerns in other treatments. However, SNV4818 is designed to be more selective, potentially reducing these risks.

For the combination of SNV4818 with fulvestrant, specific safety information is also limited. Fulvestrant, a standard treatment for certain types of cancer, has a well-known safety profile. The focus is on how SNV4818 interacts with it and whether it introduces any new safety concerns.

As this trial is in its early phase, it primarily assesses safety. The trial is closely monitored for side effects, and adjustments are made to ensure participant safety. Participants in these early trials help researchers learn about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SNV4818 for cancer because it offers a novel approach to treatment. Unlike standard treatments like chemotherapy, which broadly attack rapidly dividing cells, SNV4818 is designed to precisely target cancer cells, potentially reducing side effects. The study explores SNV4818 both as a standalone treatment and in combination with Fulvestrant, an established therapy, which could enhance its effectiveness against hormone-sensitive cancers. This targeted action and combination strategy could lead to more efficient and better-tolerated treatment options for patients.

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

Research has shown that SNV4818 targets certain proteins that may help fight cancer, potentially making it effective for treating solid tumors. This trial will evaluate SNV4818 both as a monotherapy and in combination with Fulvestrant, a treatment for some breast cancers.

Participants in the SNV4818+Fulvestrant combination arm may benefit from the potential enhanced effectiveness of the combination, as researchers hope it might work better than either treatment alone. Past studies have shown that Fulvestrant can prevent disease progression for about 3.18 months. Although SNV4818 remains in the early stages of research, its potential to work with Fulvestrant makes it a promising option for people with advanced cancers. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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SNV4818 in Participants With Advanced Solid Tumors

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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 ...

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SNV4818 for Cancer

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 ...

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SNV-4818 - Drug Targets, Indications, Patents

The first protein most likely drives the therapies' efficacy to treat cancer, while scientists believe the second triggers the haematological toxicities that ...

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Synnovation Therapeutics Announces Second Program to ...

"SNV4818 has the potential to address a significant unmet need for a large population of patients with breast cancer and multiple other tumor ...

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First Patient Dosed in Phase I Trial with SNV4818 ...

“SNV4818 has the potential to address a significant unmet need for a large population of patients with breast cancer and multiple other tumor ...