RO7589831 for Solid Tumors

Recruiting at 33 trial locations

Overseen By Vividion Clinical Trial Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: CNS metastases, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

295 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called VVD-133214 (also known as RO7589831), a pill designed to block the growth of certain cancer types by targeting a protein linked to cancer growth. It targets individuals with advanced solid tumors that are difficult to remove or have spread, specifically those with tumors showing microsatellite instability (MSI) or deficient mismatch repair (dMMR), markers that can lead to cancer. The trial will test VVD-133214 alone and in combination with another drug, pembrolizumab, to assess their safety and effectiveness. For those dealing with these types of cancers who have tried standard treatments without success, this trial could be suitable. 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 treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically moderate or strong CYP3A4 inducers and inhibitors, as well as P-glycoprotein inhibitors, at least 14 days before starting the study treatment. If you are on these medications, you will need to discuss with your doctor about stopping them.

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

Research shows that RO7589831, also known as VVD-133214, is generally safe and well-tolerated in people. Early data from studies indicate it does not cause serious side effects. In earlier research with mice, the treatment was well-tolerated and helped reduce tumors in certain types of cancer.

Although this is the first time researchers are testing RO7589831 in humans, these initial results are encouraging. Participants in the trial have found the treatment manageable, and no major safety issues have been reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RO7589831 because it offers a new approach to treating solid tumors. Unlike many current treatments that rely on traditional chemotherapy or radiation, RO7589831 targets tumors at a molecular level, potentially minimizing damage to healthy cells. Additionally, when combined with pembrolizumab, an immune checkpoint inhibitor, it may enhance the immune system's ability to fight cancer more effectively. This dual approach could provide a more powerful and targeted treatment option, sparking hope for improved outcomes in patients with solid tumors.

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

Research has shown that VVD-133214, also known as RO7589831, may help treat certain advanced solid tumors. In studies, 68.8% of patients experienced disease control, meaning their cancer did not worsen. The trial includes different treatment arms, such as VVD-133214 Monotherapy and VVD-133214 combined with Pembrolizumab, to further explore its effectiveness. This drug targets a protein called Werner (WRN), often linked to the growth of cancers with specific genetic features. By blocking this protein, VVD-133214 might help stop tumor growth in these cancers. Although these findings are early, they suggest that VVD-133214 could be a valuable treatment option for patients with certain difficult-to-treat cancers. ^{2 4 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Vividion Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that are microsatellite instability (MSI) and/or deficient mismatch repair (dMMR). Participants must have measurable disease, be in good general health with a performance status score of 0 or 1, and have tried at least one standard treatment without success. They should not have any major infections, uncontrolled diabetes, CNS metastases requiring steroids or anticonvulsants, or known Werner syndrome.

Inclusion Criteria

I can provide a tissue sample from my cancer for testing.

My condition worsened after or I couldn't tolerate at least one standard treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I haven't had a serious infection or been hospitalized for one in the last 2 weeks.

I do not have uncontrolled brain metastases or cancer in the lining of my brain and spinal cord.

I do not have conditions that affect how my body absorbs food.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of RO7589831 to evaluate safety and tolerability

8-12 weeks

Monotherapy Expansion

Participants receive RO7589831 monotherapy to further evaluate safety and anti-tumor activity

12-16 weeks

Combination Expansion

Participants receive RO7589831 in combination with pembrolizumab to evaluate safety and anti-tumor activity

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RO7589831

Trial Overview The study tests RO7589831, an oral drug targeting the WRN protein to potentially stop the growth of MSI/dMMR cancers. It's a Phase I trial involving dose-escalation and expansion to assess safety, tolerability, how the body processes the drug (pharmacokinetics), its effects on cancer cells (pharmacodynamics), and initial effectiveness against tumors.

How Is the Trial Designed?

Group I: VVD-133214 Monotherapy Expansion Experimental Treatment 1 Intervention

Group II: VVD-133214 Dose Escalation Experimental Treatment 1 Intervention

Group III: VVD-133214 + Pembrolizumab Expansion Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Vividion Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

780+

Published Research Related to This Trial

The study developed a new monoclonal antibody (6D4) that effectively detects cell surface ROR1 in various cancers, including ovarian, triple-negative breast, and lung adenocarcinomas, indicating its potential as a target for cancer therapy.

However, ROR1 is also expressed in several normal tissues, raising concerns about potential on-target, off-tumor toxicities when using ROR1-targeted therapies, which necessitates careful monitoring for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. Balakrishnan, A., Goodpaster, T., Randolph-Habecker, J., et al.[2021]

The study identified Ror2 as a novel tumor-associated kinase in renal cell carcinoma (RCC), where its knockdown significantly reduced cell proliferation and induced apoptosis in RCC cells, indicating its potential role in tumor growth.

In vivo studies using nude mice showed that targeting Ror2 with shRNA plasmids significantly inhibited tumor growth, suggesting that Ror2 could be a promising therapeutic target for RCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ror2, a Developmentally Regulated Kinase, Is Associated With Tumor Growth, Apoptosis, Migration, and Invasion in Renal Cell Carcinoma. Yang, CM., Ji, S., Li, Y., et al.[2021]

ROR1 CAR-T cells, designed to target a specific cancer marker found in various solid tumors, showed effective tumor control in mouse models without causing severe toxicity, indicating a promising safety profile.

Among the two ROR1 CARs tested, the one with a shorter IgG4 hinge demonstrated superior functionality and surface expression, suggesting that modifications in CAR design can enhance therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing ROR1 Targeting CAR-T Cells against Solid Tumors in Preclinical Studies. Lee, BK., Wan, Y., Chin, ZL., et al.[2022]

The study successfully developed a chimeric antigen receptor T cell (CAR-T) targeting ROR1, demonstrating a 47.23% infection efficiency in tumor cells.

The CAR-T cells specifically killed ROR1-positive tumor cells and significantly increased the release of interferon-gamma (IFN-γ), indicating a strong immune response, which supports its potential for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Construction of ROR1 Targeting Chimeric Antigen Receptor Modified T Cells and Its Killing Effect for ROR1-positive Tumor Cells]. Chen, Y., Mo, ZM., Qin, DY., et al.[2019]

ROR1 is significantly overexpressed in colorectal carcinoma (CRC) tissues compared to adjacent non-tumor tissues, and its expression correlates with larger tumor size and advanced disease stages (III and IV).

Down-regulating ROR1 in CRC cells led to reduced cell proliferation and increased apoptosis, suggesting that targeting ROR1 could be a potential therapeutic strategy in treating colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Down-regulation of receptor-tyrosine-kinase-like orphan receptor 1 suppresses cell growth and enhances apoptosis in human colorectal carcinoma]. Ma, W., He, X., Zhang, H., et al.[2016]

Citations

1. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.5c01805

Identification of VVD-214/RO7589831, a Clinical-Stage ... Treatment with 100 mg/kg resulted in tumor stasis (tumor growth inhibition (TGI) = 98%), while treatments with 30 mg/kg and 10 mg/kg resulted in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06004245

NCT06004245 | A Study to Evaluate the Safety, ... This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, ...

3. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT016/761432/Abstract-CT016-First-in-human-FIH-phase-1-trial-of

Abstract CT016: First-in-human (FIH) phase 1 trial of the oral ... Disease control rate (DCR) was 68.8% (95%CI 51.13, 86.37) and 20 (62.5%) pts achieved RECISTv1.1 stable disease (SD). 48.4% (15/31) of FDG-PET ...

4. vividion.com vividion.com/news/vividion-therapeutics-and-bayer-further-strengthen-oncology-development-pipeline-with-clinical-stage-wrn-inhibitor/

Vividion Therapeutics and Bayer Further Strengthen ... “VVD-214 is showing promising potential to improve treatment options for patients suffering from MSI-high cancers, a population with high unmet ...

5. mdanderson.org mdanderson.org/newsroom/aacr-first-in-class-covalent-werner-helicase-inhibitor-shows-clinical-proof-of-concept-in-phase-I-trial.h00-159775656.html

AACR: First-in-class covalent Werner helicase inhibitor ... “RO7589831 appears generally safe and shows promising signals of anti-tumor efficacy,” Yap said. “These are encouraging early clinical data ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06004245

NCT06004245 | A Study to Evaluate the Safety, ... This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, ...

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/solid-tumors/a-study-to-evaluate-the-safety--pharmacokinetics--and-a-03859.html

Clinical trial for Advanced Solid Tumors-Genentech A Memb... This trial evaluates the safety and effectiveness of RO7589831, a drug that targets Werner helicase, in people with advanced solid tumors.