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A clinical trial to look at how safe and well RO7589831 works at different doses in people with advanced solid tumours, and how the body processes RO7589831
A Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of RO7589831 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
- Cancer
- Solid Tumors
- Advanced Solid Tumors
Please note that the recruitment status of the study at your site may differ from the overall study status because some study sites may recruit earlier than others.
Study Status:
Recruiting
This study runs in
Cities
- Barcelona
- Duarte
- Durham
- Houston
- Irvine
- Leuven
- London
- Louisville
- Lyon
- Madrid
- Manchester
- Nashville
- Pamplona
- Toronto
- València
- Vancouver
- Villejuif
Trial Identifier:
NCT06004245 2023-503170-20-01 BP44474
Study Summary
This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RO7589831 monotherapy, and in combination with pembrolizumab, in participants with microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) advanced solid tumors. RO7589831 is an oral drug that acts on a protein called Werner (WRN), which may promote the growth of cancers that are MSI and/or dMMR. By acting on WRN, RO7589831 may be able to block the growth of these types of cancer.
Hoffmann-La Roche
Sponsor
Phase 1
Phase
NCT06004245, BP44474, 2023-503170-20-01
Study Identifier
All
Gender
≥18 Years
Age
No
Healthy Volunteers
1. Why is the BP44474 clinical trial needed?
Solid tumours are cancer cells that grow in organ systems anywhere in the body. Standard treatment
includes surgery, chemotherapy, radiotherapy and medicines that help the body’s immune system
fight cancer (known as ‘immunotherapy’), such as anti-PD-L1 or anti-PD-1. However, treatments can cause side effects, do not work for everyone or stop working after a time, so new treatments are needed, especially for cancers that cannot be removed with surgery or that have spread to other parts of the body (known as ‘advanced solid tumours’).
Healthy and cancer cells have ways to repair themselves, because mistakes happen when a cell is dividing and growing. Some types of cancer cells have a change (mutation) called deficient mismatch repair, or dMMR, which means repairs are not done correctly, causing a type of damage known as ‘microsatellite instability’, or MSI, which kills the cell. But cancer cells with dMMR can make a protein called ‘Werner helicase’ that mends MSI so the cell can live. A drug called RO7589831 stops Werner helicase from working and may help kill cancer cells without harming healthy cells, meaning it may also cause fewer side effects than other treatments. This clinical trial is the first time that RO7589831 will be given to people.
This clinical trial aims to test the safety of RO7589831 and how well it works in people with advanced solid tumours at different doses and to understand how the body processes RO7589831.
2. How does the BP44474 clinical trial work?
This clinical trial is recruiting people with advanced solid tumours with MSI and/or dMMR. People can take part if they have had at least one previous treatment for advanced cancer that has not worked, or it caused unmanageable side effects.
People who take part in this clinical trial (participants) will be given the clinical trial treatment RO7589831 for as long as it can help them, unless they have unacceptable side effects, their cancer gets worse or they decide to leave the trial. When participants are given RO7589831 for the first time, they may need to stay in the hospital overnight for monitoring. The clinical trial doctor will see them regularly. These clinic visits will include checks to see how the participant responds to the treatment and any side effects they may have. Participants will be seen 1 month after the last dose of treatment, then every 3 months during ‘long-term follow-up’ for as long as they agree to it. The total time of participation in the clinical trial could range from 1 day to more than 2 years, including long-term follow-up. Participants can stop trial treatment and leave the clinical trial at any time.
3. What are the main endpoints of the BP44474 clinical trial?
The main clinical trial endpoints (the main results measured in the trial to see if the drug has worked) are:
The number and seriousness of any side effects
The maximum dose of RO7589831 that can be given before unacceptable side effects occur and that provides the most benefit
The other clinical trial endpoints include:
What happens to RO7589831 at different doses in the body
How the body breaks down and gets rid of RO7589831
The number of participants who have either no detectable cancer, cancer that has reduced in size or no change in their cancer, and how long the response to treatment lasts
The length of time between the start of treatment and the participants’ cancer getting worse
How long participants live
4. Who can take part in this clinical trial?
People can take part in this trial if they are at least 18 years old and have advanced solid tumours with MSI and/or dMMR that did not respond to at least one previous standard treatment (including with
anti-PD-1/PD-L1 immunotherapy if available as standard treatment for their type of cancer) or it caused unmanageable side effects. Participants may also need to allow a small sample of their cancer to be taken for testing.
People may not be able to take part in this trial if they have uncontrolled cancer that has spread to the brain or spinal cord; have or have had a second type of cancer within the last 2 years; have certain infections, uncontrolled diabetes, or heart or lung disease; or are not able to swallow pills. People who have had any treatment before that affects the activity of Werner helicase or who have Werner syndrome will not be able to take part.
5. What treatment will participants be given in this clinical trial?
Everyone who joins this clinical trial will be given RO7589831 as a pill to take once or twice every day at home, or at the clinic if they are attending a scheduled clinic visit that day.
This is an open-label trial, which means everyone involved, including the participant and the clinical trial doctor, will know the clinical trial treatment the participant has been given.
6. Are there any risks or benefits in taking part in this clinical trial?
The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People who would like to participate will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial).
Risks associated with the clinical trial drug
Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drug used in this clinical trial. Side effects can be mild to severe, even life-threatening, and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly.
RO7589831 has not yet been tested in humans. For this reason, this drug’s side effects are not known now. Participants will be told about the possible side effects based on laboratory studies or knowledge of similar drugs. RO7589831 will be given as an oral pill (given by mouth). Participants will be told about any known side effects of swallowing pills.
Potential benefits associated with the clinical trial
Participants’ health may or may not improve from participation in the clinical trial. Still, the information collected may help other people with similar medical conditions in the future.
Study Summary
This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RO7589831 monotherapy, and in combination with pembrolizumab, in participants with microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) advanced solid tumors. RO7589831 is an oral drug that acts on a protein called Werner (WRN), which may promote the growth of cancers that are MSI and/or dMMR. By acting on WRN, RO7589831 may be able to block the growth of these types of cancer.
Hoffmann-La Roche
Sponsor
Phase 1
Phase
NCT06004245, BP44474, 2023-503170-20-01
Trial Identifier
RO7589831
Treatments
Advanced Solid Tumors
Condition
Official Title
A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of RO7589831 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors Harboring Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR)
Eligibility Criteria
All
Gender
≥18 Years
Age
No
Healthy Volunteers
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- Have a microsatellite instability (MSI) and/or deficient mismatch repair (dMMR), histologically or cytologically documented advanced (unresectable and/or metastatic) solid tumor; for the combination with pembrolizumab only: Histologically confirmed locally advanced, or metastatic colorectal adenocarcinoma (CRC) with no prior systemic treatment for metastatic disease and not amenable to surgery
- Have received and then progressed following, or are intolerant to, standard therapy in the advanced setting
- Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Life expectancy of at least (≥)12 weeks
- Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissue for submission to Sponsor/central laboratory for retrospective central testing; for participants without archival tissue, a biopsy from either primary or metastatic tumor lesion, deemed medically feasible, must be taken
- Adequate hematologic, end-organ, and cardiovascular function, as defined in the protocol
Exclusion Criteria
- Inability or unwillingness to swallow pills
- Malabsorption syndrome or other condition that would interfere with enteral absorption
- Known hypersensitivity or intolerance to ingredients from the study drug formulation including patients with rare genetic disorders such as galactosaemia, glucose-galactose intolerance or congenital lactase deficiency
- Known uncontrolled central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) and/or carcinomatous meningitis
- Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis and atypical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds), or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 2 weeks prior to the start of drug administration (related to the completion of the course of antibiotics, except if for tumor fever) or 6 months for any intracranial abscess
- Has a positive test at screening for hepatitis B virus, hepatitis C virus, or for human immodeficiency virus (HIV), per local diagnostic standard and in accordance with local laws and regulations
- Uncontrolled diabetes or symptomatic hyperglycemia (i.e., well controlled defined as a screening hemoglobin A1c <8% and no urinary ketoacidosis)
- Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of study drug administration
- Alcohol or drug dependence or abuse
- Patients with known Werner (WRN) syndrome
- Prior treatment with any WRN helicase inhibitor
- Treatment with moderate or strong CYP3A4 inducers within 14 days prior to initiation of study treatment
- Treatment with moderate or strong CYP3A4 or P-glycoprotein inhibitors within 14 days prior to initiation of study treatment
- Pregnancy, breastfeeding, or intention of becoming pregnant during the study
Additional Exclusion Criteria for the Combination with Pembrolizumab Only:
- Active or history of autoimmune disease or immune deficiency with some exceptions
- History of interstitial lung disease or pneumonitis
- Treatment with systemic immunosuppressive medication (such as corticosteroids) within 2 weeks prior to initiation of study treatment with some exceptions
For the latest version of this information please go to www.forpatients.roche.com