RO7589831 for Solid Tumors

Recruiting at 32 trial locations

Overseen By Reference Study ID Number: BP44474 https://forpatients.roche.com/

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

Trial Summary

What is the purpose of this trial?

This trial is testing a new pill called RO7589831 for patients with specific types of advanced cancers. These cancers have certain genetic features that make them hard to treat. The pill works by blocking a protein that helps these cancers grow.

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.

How is the treatment RO7589831 different from other treatments for solid tumors?

RO7589831 is unique because it targets the ROR1 protein, which is found on the surface of certain tumor cells but not on most normal cells, making it a promising target for cancer therapy. This treatment uses a novel approach called CAR-T therapy, where T-cells are modified to specifically attack ROR1-expressing tumor cells, potentially offering a more targeted and effective treatment for solid tumors. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: RO7589831 Monotherapy Expansion Experimental Treatment 1 Intervention

Group II: RO7589831 Dose Escalation Experimental Treatment 1 Intervention

Group III: RO7589831 + 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

Findings from Research

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]

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 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]

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]

References

1. China 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]. [2019]

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

Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. [2021]

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

Ror2, a Developmentally Regulated Kinase, Is Associated With Tumor Growth, Apoptosis, Migration, and Invasion in Renal Cell Carcinoma. [2021]

4. China 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]. [2016]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Developing ROR1 Targeting CAR-T Cells against Solid Tumors in Preclinical Studies. [2022]