VVD-159642 for Solid Tumors

Recruiting at 7 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

Trial Summary

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.

What data supports the effectiveness of the drug 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 16-213 demonstrated antitumor activity in different types of cancer, including lung and ovarian cancer, and was found to enhance the effects of other cancer drugs like cisplatin in gastric cancer. ^{1 2 3 4 5}

What safety data exists for VVD-159642 (also known as VP 16-213 or etoposide) in humans?

VP 16-213, also known as etoposide, has been tested in humans and is generally well tolerated, but it can cause side effects like leukopenia (low white blood cell count), hair loss, and other blood-related issues. These side effects were observed in studies involving patients with various types of cancer, including lung cancer and leukemia. ^{1 2 5 6 7}

What makes the drug VVD-159642 unique for treating solid tumors?

VVD-159642, also known as VP 16-213 or etoposide, is unique because it is an epipodophyllotoxin derivative that works by interfering with the DNA replication process in cancer cells, particularly effective in the late S and G2 phases of cell division. It has shown significant activity in small-cell lung cancer and is often used in combination with other drugs like cisplatin to enhance its antitumor effects. ^{1 2 3 4 8}

What is the purpose of this trial?

A FIH study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of VVD-159642, a rat sarcoma viral oncogene-phosphatidylinositol 3-kinase alpha (RAS-PI3Kα) inhibitor, as a single agent and in combination with either sotorasib or trametinib in participants with advanced solid tumors.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Clinical trial of VP 16--213 (NSC 141540) I.V. twice weekly in advanced neoplastic disease: a study by the Cancer and Leukemia Group B. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. [2013]

3. Greece pubmed.ncbi.nlm.nih.gov

Etoposide enhances the antitumor effects of cisplatin in gastric cancer cells. [2013]

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

VP-16 + adriamycin vs. adriamycin alone in advanced adenocarcinoma of the breast, phase II, a randomized trial: a Southwest Oncology Group Study. [2019]

5. Greece pubmed.ncbi.nlm.nih.gov

Distribution, DNA damage and cytotoxic effects of etoposide in human tumor xenografts in vivo. [2013]

6. Japan pubmed.ncbi.nlm.nih.gov

[Phase II study of vindesine in patients with carcinoma of the lung and metastatic pulmonary tumor]. [2013]

7. Japan pubmed.ncbi.nlm.nih.gov

[A phase II study of etoposide (VP-16) injection in primary lung cancer by cooperative study group]. [2013]

8. Germany pubmed.ncbi.nlm.nih.gov

The epipodophyllotoxin derivatives VM-26 and VP-16-213, 1976-1979, a review. [2019]