VLS-1488 for Advanced Cancer

Recruiting at 14 trial locations

Overseen By Volastra Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Volastra Therapeutics, Inc.

Must not be taking: CYP3A inhibitors, MDR1 inhibitors

Disqualifiers: CNS metastases, Cardiac issues, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, VLS-1488, to determine its safety and effectiveness for people with advanced types of cancer. Researchers aim to understand how the body processes the drug and whether it helps fight cancer. The trial includes different groups to explore various doses and cancer types, including some that assess how VLS-1488 interacts with food or other drugs. Individuals with certain advanced cancers who have not found success with many standard treatments might be a good fit for this trial. As a Phase 1 trial, participants could be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions restrictions on certain medications that affect liver enzymes and drug transporters. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that VLS-1488 is likely to be safe for humans?

Research has shown that VLS-1488 is safe and tolerable for patients. One study found that patients with advanced cancers tolerated the treatment well, with no major safety issues reported.

Early results also demonstrated some anti-tumor activity, suggesting the treatment might help stop cancer growth. The FDA granted VLS-1488 fast track status, allowing for quicker approval if positive results continue.

Overall, VLS-1488 appears promising in terms of safety, but further research is needed to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about VLS-1488 for advanced cancer because it offers a fresh approach to treatment. Unlike traditional cancer therapies that often rely on chemotherapy or radiation to kill rapidly dividing cells, VLS-1488 is designed to explore new dosing strategies and assess its interaction with other drugs and food. This could lead to more personalized and effective treatment plans. Additionally, the focus on different tumor types and dose levels in the trial may help identify the most promising scenarios for this drug's use, potentially broadening its application across various cancers.

What evidence suggests that VLS-1488 might be an effective treatment for advanced cancer?

Research has shown that VLS-1488, a new cancer treatment, yields promising results for advanced cancers. In an earlier study, 7 out of 17 patients with advanced ovarian cancer, who had already tried many treatments, experienced tumor shrinkage. This finding suggests that VLS-1488 might help reduce tumors in patients who have undergone extensive treatment. Early data also indicate that the treatment is safe and manageable, with positive effects, especially for high-grade serous ovarian cancer. The FDA has granted it fast track status, recognizing its potential benefits for patients with ovarian cancer that doesn't respond to standard treatments. Participants in this trial will enroll in various treatment arms to explore different doses and tumor types, further examining the efficacy and safety of VLS-1488. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced cancers who've already tried standard treatments. They should be able to perform daily activities with minimal assistance (ECOG ≤ 1), have measurable disease, and take pills without changing them. Not eligible if they have certain genetic mutations, brain metastases, previous KIF18A inhibitor treatment, or recent serious heart issues.

Inclusion Criteria

I have at least one tumor that can be measured on a CT scan or MRI.

I have no other treatment options that would significantly help my cancer.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had fluid drained from my abdomen or chest in the last 28 days.

I can avoid medications that strongly affect certain liver enzymes and drug transporters.

I have not had a bowel blockage or gut tear in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Examine the safety and tolerability of VLS-1488 in different solid tumor types at various dose levels to identify the Maximum Tolerated Dose (MTD)

28-day cycles

Dose Expansion

Examine the safety, tolerability, Drug Drug Interaction (DDI) risk, Food Effect (FE), and preliminary efficacy of VLS-1488 in different tumor types and/or dose levels

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VLS-1488

Trial Overview The study tests VLS-1488's safety and early effectiveness in patients with various advanced cancers. It includes two parts: dose escalation to find the right amount of drug and dose expansion to see how well it works at that dose.

How Is the Trial Designed?

Group I: Dose Expansion: Exploration Cohorts Experimental Treatment 1 Intervention

Subjects with a selected single tumor type will be randomized 1:1 into Exploration Cohorts at two or more dose levels of interest. A subset of subjects will have additional assessments to examine the potential for VLS-1488 to interact with other drugs and the effect of food on VLS-1488 absorption.

Group II: Dose Expansion: Development Cohorts Experimental Treatment 1 Intervention

Subjects with other tumor types will be enrolled at a single dose level of interest. These Development Cohorts will be utilized to examine the preliminary efficacy of VLS-1488 in various tumor types.

Group III: Dose Escalation: Dose Escalation Cohorts Experimental Treatment 1 Intervention

Subjects will be enrolled at various doses and/or schedules of VLS-1488. These Dose Escalation Cohorts will be utilized to identify the MTD and to select dose levels for Dose Expansion.

Group IV: Dose Escalation: Backfill Cohorts Experimental Treatment 1 Intervention

Additional subjects may be enrolled at any dose level that does not meet de-escalation or elimination rules per the BOIN design. These Backfill Cohorts will be utilized to build additional data to support selection of doses and/or tumor types for further study in Dose Expansion.

VLS-1488 is already approved in United States for the following indications:

Approved in United States as VLS-1488 for:

• None approved yet; Fast Track designation for platinum-resistant high-grade serous ovarian cancer

Who Is Running the Clinical Trial?

Volastra Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

310+

Published Research Related to This Trial

The combination of vandetanib and bicalutamide in patients with metastatic castration-resistant prostate cancer did not show superior efficacy compared to bicalutamide alone, with similar PSA response rates of 18% for the combination and 19% for bicalutamide alone.

Patients receiving the combination therapy experienced significantly higher rates of treatment discontinuation due to adverse events (42% vs. 5%), indicating that the combination is associated with considerable toxicity and is not recommended for further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naïve castration-resistant prostate cancer. Azad, AA., Beardsley, EK., Hotte, SJ., et al.[2022]

Cediranib, when combined with standard chemotherapy (cisplatin and gemcitabine), showed promising anti-tumor activity in advanced non-small cell lung cancer, with a response rate of 26.7% among all patients and 33.3% among those evaluable.

The study found that cediranib can be safely administered at a daily dose of 30 mg without dose-limiting toxicities, although some manageable side effects like fatigue and diarrhea were noted, indicating its potential for further development in phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. Goss, G., Shepherd, FA., Laurie, S., et al.[2022]

In a phase II trial involving 104 patients with advanced non-small-cell lung cancer (NSCLC), the addition of the vascular disrupting agent ASA404 to standard chemotherapy showed numerical improvements in tumor response, time to disease progression, and overall survival without significantly increasing side effects.

The study supports the potential of combining VDAs like ASA404 with standard chemotherapy, as they target different aspects of tumor biology, and further trials are ongoing to explore this combination's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials of vascular disrupting agents in advanced non--small-cell lung cancer. McKeage, MJ.[2012]

In a study of 310 cancer patients, adding mistletoe (Viscum album L.) to targeted therapy significantly reduced the frequency of adverse events (AEs) and treatment discontinuation rates compared to targeted therapy alone.

Patients receiving the combination therapy had a 70% lower probability of discontinuing their oncological treatment due to AEs, highlighting the potential of mistletoe as a supportive treatment in cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Safety of Combined Targeted and Viscum album L. Therapy in Oncological Patients. Thronicke, A., Oei, SL., Merkle, A., et al.[2020]

The maximum tolerated dose (MTD) of motesanib when combined with gemcitabine and erlotinib was determined to be 100 mg once daily, indicating a safe dosage for further studies.

Among the 56 patients treated, motesanib showed tolerable safety with common side effects like diarrhea and nausea, and resulted in one confirmed partial response and 26 patients with stable disease, suggesting potential efficacy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study. Kotasek, D., Tebbutt, N., Desai, J., et al.[2022]

In a systematic review of 17 randomized controlled trials involving 6,982 patients with solid tumors, VEGFR2-targeted agents were found to have an overall incidence of fatal adverse events (FAEs) of only 1.7%.

The study concluded that the use of VEGFR2-targeted agents did not significantly increase the risk of FAEs compared to control treatments, indicating a favorable safety profile for these cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and Risk of Fatal Adverse Events in Cancer Patients Treated With Vascular Endothelial Growth Factor Receptor 2-Targeted Agents: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials. Zhao, B., Zhao, H., Zhao, J.[2020]

A meta-analysis of 10 randomized controlled trials involving 4,679 cancer patients found that vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are associated with a 1.5% incidence of fatal adverse events (FAEs), which is significantly higher than in control patients.

The relative risk of experiencing FAEs for patients treated with VEGFR TKIs was 2.23, indicating more than double the risk compared to those not receiving these treatments, highlighting the need for careful monitoring of patients on these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. Schutz, FA., Je, Y., Richards, CJ., et al.[2022]

In a clinical trial involving 276 patients with HER2-negative metastatic breast cancer, treatment with motesanib plus paclitaxel did not show a significant improvement in objective response rate compared to placebo plus paclitaxel, with response rates of 49% and 41% respectively.

Motesanib was associated with a higher incidence of serious adverse events, particularly gastrointestinal issues, compared to the placebo and bevacizumab groups, leading to the conclusion that further investigation of motesanib at this dose and schedule is not supported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a phase 2, randomised, double-blind, placebo-controlled study. Martin, M., Roche, H., Pinter, T., et al.[2022]

In a study involving 12,520 patients from 23 randomized controlled trials, VEGFR-TKIs significantly improved progression-free survival (PFS), objective response rates (ORR), and disease control rates (DCR) in advanced non-small cell lung cancer (NSCLC) patients, but did not significantly affect overall survival (OS).

Patients treated with VEGFR-TKIs experienced a higher incidence of adverse events, including serious conditions like neutropenia and hypertension, indicating that while these drugs can be effective, they also come with increased risks of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are VEGFR-TKIs effective or safe for patients with advanced non-small cell lung cancer? Wang, S., Yang, Z., Wang, Z.[2022]

Bevacizumab is the only FDA-approved antiangiogenic therapy for advanced non-small-cell lung cancer (NSCLC), but it carries risks such as hemorrhage, venous thromboembolism, hypertension, and proteinuria based on accumulated safety data.

New investigational agents like aflibercept and multitargeted tyrosine kinase inhibitors (TKIs) are being developed to target angiogenesis through different mechanisms, with emerging safety profiles that may offer additional treatment options for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile and tolerability of antiangiogenic agents in non-small-cell lung cancer. Gadgeel, SM.[2022]

Citations

1. volastratx.com volastratx.com/initial-data-from-first-in-human-phase-i-ii-trial-of-novel-kif18a-inhibitor-vls-1488/

Volastra Announces Initial Data from First-in-Human Phase ... Novel once-daily oral KIF18A inhibitor demonstrated tumor reduction in 7 of 17 heavily pre-treated advanced ovarian cancer patients enrolled in dose escalation.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3012

Preliminary results from a first-in-human, phase I/II study of ... Conclusions: VLS-1488 was found to be safe and tolerable, with encouraging anti-tumor activity observed in heavily treated HGSOC pts. VLS-1488 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05902988

NCT05902988 | A Phase I/II Study of VLS-1488 in Subjects ... This is a first-in-human phase I/II study to examine the safety, tolerability and preliminary efficacy of VLS-1488 in subjects with advanced cancers.

4. targetedonc.com targetedonc.com/view/vls-1488-gains-fda-fast-track-status-in-advanced-ovarian-cancer

VLS-1488 Gains FDA Fast Track Status in Advanced ... The FDA has granted VLS-1488 fast track designation in patients with platinum-resistant high-grade serous ovarian cancer.

5. onclive.com onclive.com/view/fda-grants-fast-track-status-to-vls-1488-for-platinum-resistant-high-grade-serous-ovarian-cancer

FDA Grants Fast Track Status to VLS-1488 for Platinum- ... The KIF18A inhibitor VLS-1488 has received fast track designation from the FDA for platinum-resistant high-grade serous ovarian cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05902988

NCT05902988 | A Phase I/II Study of VLS-1488 in Subjects ... This is a first-in-human phase I/II study to examine the safety, tolerability and preliminary efficacy of VLS-1488 in subjects with advanced cancers. Detailed ...