VVD-159642 for Solid Tumors

Recruiting at 8 trial locations

Overseen By Vividion Clinical Trial Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vividion Therapeutics, Inc.

Disqualifiers: CNS malignancies, Cardiac diseases, Hypertension, Hepatitis B, others

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

Compensation: Varies

Number of Visits: Unknown

220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, VVD-159642, for individuals with advanced solid tumors. Researchers aim to assess its safety and effectiveness both alone and in combination with other drugs like sotorasib and trametinib. Individuals with certain cancers, such as pancreatic, lung, or colorectal cancer, or tumors with specific gene changes, may qualify. Participants must have tumors that are inoperable or have metastasized. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

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

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

Earlier research has shown that VVD-159642 can slow tumor growth in lab studies without causing major side effects related to the drug's mechanism. This suggests it might be gentler on the body compared to some other treatments.

The current study is in its early stages, primarily focusing on assessing the treatment's safety. Researchers closely monitor for any unwanted side effects to ensure the treatment is safe for participants. Although there is limited human data, its testing in people indicates it has passed initial lab safety tests with encouraging results.

When VVD-159642 is combined with other drugs like sotorasib or trametinib, the study will also evaluate the safety and tolerability of these combinations. Both sotorasib and trametinib have established safety profiles, but the main focus will be on how well participants tolerate the new combination with VVD-159642. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VVD-159642 for solid tumors because it offers a new approach to treatment. Unlike traditional chemotherapy that targets rapidly dividing cells, VVD-159642 works by a novel mechanism that may target specific pathways involved in tumor growth. This treatment is also being tested in combination with sotorasib and trametinib, both of which are known to target specific mutations in cancer cells, potentially enhancing its effectiveness. The ability to combine VVD-159642 with these targeted therapies could lead to more personalized and effective treatment options for patients.

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

Studies have shown that VVD-159642 may slow tumor growth in some cancer types by targeting specific parts of cancer cells. Early tests suggest it works well with minimal side effects. In this trial, one group will receive VVD-159642 alone, while another will receive VVD-159642 with sotorasib, a drug for certain lung cancers, potentially enhancing the treatment's effectiveness. A third group will receive VVD-159642 with trametinib, a drug for skin cancer, which may boost its cancer-fighting effects. This combination approach aims to block cancer's growth signals from multiple directions, potentially increasing the treatment's effectiveness. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be surgically removed or have spread, and who are in good physical condition (ECOG ≤1). They must have a type of tumor with specific genetic changes (RAS alterations or EGFR/HER2 overexpression) and should be able to take pills. People with pancreatic, colorectal, lung cancer, or any RAS-altered solid tumor are especially considered.

Inclusion Criteria

My cancer can be measured by standard imaging tests.

My blood, kidney, and liver tests meet the study's requirements.

I can take pills by mouth.

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-159642, orally, daily in 21-day treatment cycles

21 days per cycle, up to 29 months

Dose Expansion

Participants receive VVD-159642 at the recommended dose for expansion, orally, daily in 21-day treatment cycles, with options for combination with sotorasib or trametinib

21 days per cycle, up to 29 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VVD-159642

Trial Overview The study tests VVD-159642 alone and combined with sotorasib or trametinib. It's a first-in-human trial focusing on safety, how the body processes the drug (PK), its effects on the body (PD), and initial effectiveness against various advanced solid tumors.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib Experimental Treatment 2 Interventions

Participants will receive VVD-159642 at RDE orally, daily in combination with trametinib, in 21-day treatment cycles after a safety run-in.

Group II: Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib Experimental Treatment 2 Interventions

Participants will receive VVD-159642 at RDE orally, daily in combination with sotorasib, in 21-day treatment cycles after a safety run-in.

Group III: Part 2: Dose Expansion (Cohort A): VVD-159642 Single Agent Experimental Treatment 1 Intervention

Participants will receive VVD-159642 at the recommended dose for expansion (RDE), orally, daily in 21-day treatment cycles during Part 2.

Group IV: Part 1: Dose Escalation: VVD-159642 Single Agent Experimental Treatment 1 Intervention

Participants will receive ascending doses of VVD-159642, orally, daily in 21-day treatment cycles during Part 1.

Who Is Running the Clinical Trial?

Vividion Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

780+

Published Research Related to This Trial

VP 16-213, a new semisynthetic epipodophyllotoxin, demonstrated clinically valuable antitumor activity in a phase II trial involving 33 patients with solid tumors and acute leukemias, particularly showing promising results in patients with oat cell carcinoma of the lung.

The drug was generally well tolerated, but it commonly caused side effects like leukothrombopenia and hair loss, indicating a need for further studies to optimize its dosage and explore its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. Jungi, WF., Senn, HJ., Beckmann, C., et al.[2013]

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]

The combination of cisplatin (CDDP) and etoposide (VP-16) demonstrated synergistic antitumor effects in both an established gastric cancer cell line (KATO-III) and fresh tumor cells from 55 gastric cancer patients, indicating its potential effectiveness in treating this type of cancer.

The study found that the antitumor effects of CDDP were enhanced by early exposure to VP-16, particularly in poorly differentiated gastric cancer cells, suggesting that this combination therapy could be especially beneficial for patients with more aggressive cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide enhances the antitumor effects of cisplatin in gastric cancer cells. Hotta, T., Tanimura, H., Yamaue, H., et al.[2013]

Citations

1. vividion.com vividion.com/news/vividion-therapeutics-doses-first-patient-in-phase-i-study-of-ras-pi3k%CE%B1-inhibitor-for-treatment-of-advanced-solid-tumors/

Vividion Therapeutics Doses First Patient in Phase I Study ... Preclinical studies of VVD-159642 give us confidence in its potential to inhibit tumor growth while avoiding the on-target toxicities that ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06804824

NCT06804824 | A First-in-Human (FIH) Study to Evaluate ... A FIH study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of VVD-159642.

3. withpower.com withpower.com/trial/phase-1-neoplasms-2-2025-d278a

VVD-159642 for Solid Tumors The drug VVD-159642, which may be related to VP 16-213 (also known as etoposide), has shown some effectiveness in treating various cancers. In studies, VP 16- ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/vividion-trial-cancer-treatment/

Vividion begins subject dosing in trial of cancer treatment Vividion Therapeutics has dosed the first subject in a Phase I trial of an oral inhibitor, VVD-159642, aimed at treating rat sarcoma (RAS)-driven cancers.

5. finance.yahoo.com finance.yahoo.com/news/bayers-vividion-initiates-dosing-early-174500067.html

Bayer's Vividion Initiates Dosing in Early-Stage Cancer Study BAYRY subsidiary Vividion Therapeutics doses the first patient in a phase I study on VVD-159642 to treat advanced solid tumors.

6. clin.larvol.com clin.larvol.com/trial-detail/NCT06804824

A First-in-Human (FIH) Study to Evaluate the Safety and ... A first-in-human (FIH) study to evaluate the safety and tolerability of VVD-159642 in participants with advanced solid tumors.