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

Advanced Solid Tumors Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06004245
• Other study ID #: BP44474
• Secondary ID: 2023-503170-20-0
• Status: Recruiting
• Phase: Phase 1
• Start date: January 25, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BP44474 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: December 31, 2026
• Est. primary completion date: December 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Microsatellite Instability

Intervention

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

Locations

Country	Name	City	State
Belgium	UZ Leuven Gasthuisberg	Leuven
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
Denmark	Rigshospitalet; Onkologisk Klinik	København Ø
France	CLCC Leon Berard Lyon	Lyon
France	Gustave Roussy	Villejuif
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Clinica Universidad de Navarra Madrid; Servicio de Oncología	Madrid
Spain	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
United Kingdom	Royal Marsden Hospital - Fulham	London
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	The Christie	Manchester
United States	City of Hope	Duarte	California
United States	Duke University; Office of Research Contracts	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	City of Hope at Irvine Lennar	Irvine	California
United States	SCRI Oncology Partners	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		From first dose of study drug until 30 days after last dose of study drug (up to approximately 15 months)
Primary	Incidence of Dose-Limiting Toxicities		Cycle 1 (1 cycle is 3 weeks)
Secondary	Maximum Plasma Concentration Observed (Cmax) of RO7589831		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)
Secondary	Time of Maximum Plasma Concentration Observed (Tmax) of RO7589831		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)
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) of RO7589831		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)
Secondary	Apparent Oral Clearance (CL/F) of RO7589831		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)
Secondary	Volume of Distribution (V/F) of RO7589831		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)
Secondary	Terminal Half-Life (T1/2) of RO7589831		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)
Secondary	Objective Response Rate		From start of study treatment until end of follow-up (up to approximately 36 months)
Secondary	Disease Control Rate		From start of study treatment until end of follow-up (up to approximately 36 months)
Secondary	Duration of Response		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)
Secondary	Progression-Free Survival, as Assessed by the Investigator		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)
Secondary	Overall Survival		From start of study treatment to the time of death from any cause (up to approximately 36 months)