VVD-130037 for Advanced Cancers

Recruiting at 24 trial locations

Overseen By Vividion Clinical Trial Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vividion Therapeutics, Inc.

Must not be taking: Anti-epileptics

Disqualifiers: Seizures, CNS metastases, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

290 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, VVD-130037, for individuals with advanced solid tumors, which are cancers that have spread or cannot be surgically removed. The trial aims to determine the optimal dose of VVD-130037 when used alone or with other cancer drugs like docetaxel and paclitaxel. Participants should have cancers that have progressed despite previous treatments, including specific types of lung, head and neck, or esophageal cancers unresponsive to standard therapies. Those with certain genetic mutations known not to benefit from this drug or with a history of seizures or specific heart conditions are not eligible. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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 anti-epileptic medications, you cannot participate in this trial.

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

Research shows that VVD-130037 is currently being tested for safety in people with advanced cancers. In earlier studies, a similar drug was used in 55 patients with advanced solid tumors, helping researchers understand how the drug might work in the body. However, since VVD-130037 is new, many unknowns about its safety remain.

For combination therapies, VVD-130037 is being tested with docetaxel and paclitaxel, common cancer treatments. The study examines how well these drugs work together and their tolerability.

This study is in the early phase of clinical trials, focusing on safety and determining the right dose. The safety profile is still under exploration, so side effects and tolerability are not fully known yet. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VVD-130037 because it offers a potential breakthrough for advanced cancers by exploring a new angle of attack. Unlike traditional chemotherapy drugs that generally target rapidly dividing cells, VVD-130037 targets specific molecular pathways unique to cancer cells. This precision could mean fewer side effects and more effective treatment. Additionally, VVD-130037 can be taken orally, which is more convenient compared to intravenous chemotherapy. When combined with standard drugs like docetaxel and paclitaxel, it could enhance the effectiveness of these existing treatments, offering new hope for patients with limited options.

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

Research has shown that VVD-130037 targets specific pathways in cells that control their response to stress and damage, which is crucial in cancer treatment as it can affect cancer cell growth and survival. Early findings suggest that VVD-130037 may effectively treat advanced solid tumors. In this trial, participants will receive VVD-130037 either alone or with docetaxel or paclitaxel. These combinations, which include well-known cancer treatments that prevent cancer cells from dividing, are under study to determine if VVD-130037 can enhance their effectiveness. Initial studies focus on understanding how well these treatments work together to combat cancer. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who have tried all standard treatments without success. They must be relatively active (ECOG ≤1), have a confirmed diagnosis, measurable disease by RECIST v1.1, and good organ/marrow function. It's not for those with certain genetic mutations or unresolved severe side effects from past cancer treatments, heart issues, seizure risks, brain metastases/spinal compression, or uncontrolled high blood pressure.

Inclusion Criteria

My cancer is confirmed to be advanced and cannot be removed by surgery.

My organs and bone marrow are functioning well.

Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the Investigator

Exclusion Criteria

I have taken medication for seizures.

I have or had cancer spread to my brain or spinal cord.

I have a history of seizures or a condition that could lead to seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ascending doses of VVD-130037, either as a single agent or in combination with docetaxel or paclitaxel, in 21-day or 28-day treatment cycles

21-28 days per cycle

Multiple visits per cycle for treatment and monitoring

Dose Expansion

Participants receive VVD-130037 at the recommended dose for expansion, either as a single agent or in combination with docetaxel or paclitaxel, in 21-day or 28-day treatment cycles

Up to approximately 4 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VVD-130037

Trial Overview

The study tests VVD-130037 to see its safety and how it affects the body and tumor growth in patients with advanced solid tumors. This first-in-human trial will also look at how the drug moves through and out of the body (pharmacokinetics) and what it does to the body (pharmacodynamics).

How Is the Trial Designed?

Group I: Part 2 (Dose Expansion): VVD-130037 and Paclitaxel Combination Therapy Experimental Treatment 2 Interventions

Participants will receive VVD-130037 at the RDE, orally, once or twice daily along with paclitaxel IV infusion administered on Days 1, 8, and 15 of each 28-day treatment cycle during Part 2.

Group II: Part 2 (Dose Expansion): VVD-130037 and Docetaxel Combination Therapy Experimental Treatment 2 Interventions

Participants will receive VVD-130037 at the RDE, orally, once or twice daily along with docetaxel IV infusion administered once every 3 weeks in 21-day treatment cycles during Part 2.

Group III: Part 2 (Dose Expansion): VVD-130037 Single Agent Experimental Treatment 1 Intervention

Participants will receive VVD-130037 at the recommended dose for expansion (RDE), orally, once or twice daily in 21-day treatment cycles during Part 2.

Group IV: Part 1 (Dose Escalation): VVD-130037 and Paclitaxel Combination Therapy Experimental Treatment 2 Interventions

Participants will receive ascending doses of VVD-130037, orally, once or twice daily along with paclitaxel IV infusion administered on Days 1, 8, and 15 of each 28-day treatment cycle during Part 1.

Group V: Part 1 (Dose Escalation): VVD-130037 and Docetaxel Combination Therapy Experimental Treatment 2 Interventions

Participants will receive ascending doses of VVD-130037, orally, once or twice daily along with docetaxel intravenous (IV) infusion administered once every 3 weeks in 21-day treatment cycles during Part 1.

Group VI: Part 1 (Dose Escalation): VVD-130037 Single Agent Experimental Treatment 1 Intervention

Participants will receive ascending doses of VVD-130037, orally, once or twice daily in 21-day treatment cycles during Part 1.

Group VII: Experimental: Part 2 (Dose Expansion): VVD-130037 and Pembrolizumab Combination Therapy Experimental Treatment 2 Interventions

Participants will first be evaluated in a safety-run in cohort to determine the RDE(s). Participants will then receive VVD-130037 at the RDE, orally, once or twice daily along with pembrolizumab IV infusion administered once every 3 weeks in 21-day treatment cycles during Part 2.

Who Is Running the Clinical Trial?

Vividion Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

780+

Published Research Related to This Trial

The maximum tolerated dose (MTD) of veliparib when combined with pegylated liposomal doxorubicin (PLD) and carboplatin for treating recurrent ovarian cancer is determined to be 80 mg taken twice daily, with myelosuppression identified as a dose-limiting toxicity (DLT).

In patients receiving the combination of veliparib and bevacizumab, 75% experienced DLTs, including severe thrombocytopenia and hypertension, indicating that lower doses of veliparib may be necessary when used with platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG Oncology/Gynecologic Oncology Group study. Landrum, LM., Brady, WE., Armstrong, DK., et al.[2022]

The combination of ZD9331 and cisplatin was well tolerated at a dose of 130/50 mg/m², with dose-limiting toxicities including neutropenia and thrombocytopenia, indicating a manageable safety profile for this regimen.

Among the 15 patients evaluated, 2 experienced a partial response to treatment, and 6 had stable disease, suggesting that this combination therapy may have preliminary antitumor activity in patients with refractory solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of the antifolate ZD9331 in combination with cisplatin in patients with refractory solid malignancies. Bilenker, JH., Stevenson, JP., Flaherty, KT., et al.[2013]

A series of novel VEGFR-2 inhibitors were discovered, with compound 23 showing superior antiproliferative effects compared to FDA-approved drugs like sorafenib and sunitinib across nine tumor types.

Compound 23 demonstrated high potency against drug-resistant cancer cell lines, suggesting it could be a promising treatment option for various cancers, including leukemia, NSCLC, colon, ovarian, and breast cancer, while maintaining a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of Novel Potent VEGFR-2 Inhibitors Exerting Significant Antiproliferative Activity against Cancer Cell Lines. Zhang, Y., Chen, Y., Zhang, D., et al.[2019]

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]

In a Phase I/II trial involving 12 patients with advanced non-small cell lung cancer (NSCLC), the combination of cisplatin and vinorelbine showed a maximum tolerated dose of 8 mg/m² for vinorelbine, administered as a bolus followed by a continuous infusion, resulting in a 50% overall response rate.

The treatment demonstrated manageable toxicity, with febrile neutropenia and grade 3 mucositis as dose-limiting toxicities, but less neurotoxicity compared to traditional weekly bolus schemes, indicating a potentially safer administration method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin plus continuous infusion vinorelbine for the treatment of advanced non-small cell lung cancer: a phase I-II study. Cobo-Dols, M., Gil-Calle, S., Villar-Chamorro, E., et al.[2019]

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]

The combination of navelbine (NVB) and cisplatin (CDDP) showed a synergistic effect on killing lung adenocarcinoma cells when NVB was administered before CDDP, indicating a potentially more effective treatment strategy compared to using vindesine (VDS) with CDDP.

Both NVB and VDS caused cell cycle arrest in the G2M phase, while CDDP led to S phase accumulation, suggesting different mechanisms of action that could be exploited for enhanced therapeutic effects in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetic analysis of combination effect of navelbine (KW-2307) with cisplatin against human lung adenocarcinoma PC-12 cells in culture. Gomi, K., Ohno, H., Nomura, K., et al.[2019]

The neoadjuvant chemotherapy regimen of ifosfamide, cisplatin, and etoposide (VIP) followed by concomitant thoracic radiotherapy was found to be feasible for treating locally advanced non-small cell lung cancer (NSCLC), with a 61% objective response rate by the end of radiotherapy.

However, the treatment was associated with significant toxicities, including myelosuppression and acute esophagitis, leading to hospital readmissions for 23 patients, which raises concerns about the safety and limits the further development of this aggressive treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant etoposide, ifosfamide, and cisplatin followed by concomitant thoracic radiotherapy and continuous cisplatin infusion in stage IIIb non-small cell lung cancer. Pujol, JL., Lafontaine, T., Quantin, X., et al.[2019]

In a study of 76 patients with advanced non-small-cell lung cancer (NSCLC), the chemotherapy combination of vinorelbine, ifosfamide, and cisplatin resulted in a 51% overall response rate, indicating its potential effectiveness in treating this condition.

The treatment was associated with manageable toxicities, primarily leukopenia, with 26% of cycles experiencing severe neutropenia, suggesting that while the regimen is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of vinorelbine/ifosfamide/cisplatin for the treatment of advanced non-small-cell lung cancer. Baldini, E., Tibaldi, C., Chella, A., et al.[2020]

Dilpacimab, a dual-variable domain immunoglobulin targeting DLL4 and VEGF pathways, showed an acceptable safety profile in a phase I study with 55 patients, where common side effects included hypertension (60%) and headache (30.9%).

The study established a recommended phase II dose of 3.75 mg/kg, with preliminary efficacy showing a partial response in 10.9% of patients, particularly in ovarian cancer, indicating potential clinical activity in advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Open-Label Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Dilpacimab in Patients with Advanced Solid Tumors. Gordon, MS., Nemunaitis, J., Barve, M., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05954312

NCT05954312 | A First-in-Human (FIH) Study to Evaluate ...

A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130037 in Participants With Advanced Solid Tumors. ClinicalTrials.gov ID NCT05954312.

2.

withpower.com

withpower.com/trial/phase-1-neoplasms-6-2023-528e1

VVD-130037 for Advanced Cancers

This trial tests a new drug, VVD-130037, for safety and effectiveness in patients with advanced solid tumors. It will study how the drug moves through and ...

3.

bayer.com

bayer.com/en/us/news-stories/vividion-therapeutics-oncology-clinical-trial

Vividion Therapeutics starts Phase I clinical trial in ...

The Phase I clinical trial will evaluate the safety, pharmacokinetics and pharmacodynamics and preliminary efficacy of VVD-130037 in patients ...

4.

synapse.patsnap.com

synapse.patsnap.com/blog/the-journey-of-vvd-130037-in-targeting-keap1-x-nrf2-pathways-for-solid-neoplasms

The Journey of VVD-130037 in Targeting KEAP1 x Nrf2 ...

The drug VVD-130037 is a small molecule drug developed to target the KEAP1 x Nrf2 pathways in the treatment of neoplasms, specifically advanced malignant solid ...

5.

careacross.com

careacross.com/clinical-trials/trial/NCT05954312

A First-in-Human (FIH) Study to Evaluate the Safety and ...

Summary: A FIH study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of VVD-130037 in participants with advanced solid ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05954312?term=NCT05954312&rank=1

NCT05954312 | A First-in-Human (FIH) Study to Evaluate ...

A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130037 in Participants With Advanced Solid Tumors. ClinicalTrials.gov ID ...

7.

medchemexpress.com

medchemexpress.com/vvd-130037.html?srsltid=AfmBOorNbJAPlVriQOLIqZbgHSn93q1BAUlVItThXEIKbUSX_XxJjlcD

VVD-130037 (BAY-3605349) | Keap1-Nrf2 Activator

VVD-130037 degrades NRF2 (nuclear factor-erythroid 2 p45-related factor 2), resulting in significant inhibition of tumor growth in advanced solid tumors.