A Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of RO7589831 in Participants With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT06004245
• Recruitment Status: Recruiting
• First Posted: August 22, 2023
• Last Update Posted: May 14, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: August 16, 2023
• First Posted Date: August 22, 2023
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: January 25, 2024
• Estimated Primary Completion Date: December 22, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 16, 2023)

• Incidence of Adverse Events, with Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) [ Time Frame: From first dose of study drug until 30 days after last dose of study drug (up to approximately 15 months) ]
• Incidence of Dose-Limiting Toxicities [ Time Frame: Cycle 1 (1 cycle is 3 weeks) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 16, 2023)

• Maximum Plasma Concentration Observed (Cmax) of RO7589831 [ Time Frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months) ]
• Time of Maximum Plasma Concentration Observed (Tmax) of RO7589831 [ Time Frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months) ]
• Area Under the Plasma Concentration-Time Curve (AUC) of RO7589831 [ Time Frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months) ]
• Apparent Oral Clearance (CL/F) of RO7589831 [ Time Frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months) ]
• Volume of Distribution (V/F) of RO7589831 [ Time Frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months) ]
• Terminal Half-Life (T1/2) of RO7589831 [ Time Frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months) ]
• Objective Response Rate [ Time Frame: From start of study treatment until end of follow-up (up to approximately 36 months) ]
• Disease Control Rate [ Time Frame: From start of study treatment until end of follow-up (up to approximately 36 months) ]
• Duration of Response [ Time Frame: From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months) ]
• Progression-Free Survival, as Assessed by the Investigator [ Time Frame: From start of study treatment to the first occurrence of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months) ]
• Overall Survival [ Time Frame: From start of study treatment to the time of death from any cause (up to approximately 36 months) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of RO7589831 in Participants With Advanced Solid Tumors
• Official Title: A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of RO7589831 in Participants With Advanced Solid Tumors Harboring Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR)
• Brief 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 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

This is an open label study. Participants will be assigned to dose cohorts in the order in which they are enrolled. However, if two or more cohorts in the same part of the study are open for enrollment at the same time, participants will be randomized into these cohorts.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Advanced Solid Tumors

Intervention

Drug: RO7589831

RO7589831 will be administered orally and once daily (QD) in 3-week cycles.

Study Arms

• Experimental: Part I: RO7589831 Dose Escalation
  Intervention: Drug: RO7589831
• Experimental: Part II: RO7589831 Dose Expansion
  Intervention: Drug: RO7589831

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 16, 2023): 220
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: December 22, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Have a locally confirmed microsatellite instability (MSI) and/or deficient mismatch repair (dMMR), histologically or cytologically documented advanced (unresectable and/or metastatic) solid tumor
• Have received and then progressed following or are intolerant to at least 1 standard treatment regimen 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)
• Alcohol or drug dependence or abuse
• Patients with known Werner (WRN) syndrome
• Prior treatment with any WRN helicase inhibitor
• Pregnancy, breastfeeding, or intention of becoming pregnant during the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: BP44474 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

• Listed Location Countries: Belgium, Canada, Denmark, France, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT06004245
• Other Study ID Numbers: BP44474; 2023-503170-20-00 ( Registry Identifier: EU Trial Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

Plan Description

For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

Roche's Global Policy on the Sharing of Clinical Information describes studies which are eligible for data sharing and how to request access (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2024