Trial Title:
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
NCT ID:
NCT06004245
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Microsatellite Instability
Pembrolizumab
Conditions: Keywords:
Deficient mismatch repair
dMMR
Microsatellite instability
MSI
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
RO7589831
Description:
RO7589831 will be administered orally and once daily (QD) in 3-week cycles.
Arm group label:
RO7589831 + Pembrolizumab Expansion
Arm group label:
RO7589831 Dose Escalation
Arm group label:
RO7589831 Monotherapy Expansion
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg
on Day 1 of each 21-day cycle.
Arm group label:
RO7589831 + Pembrolizumab Expansion
Other name:
KEYTRUDA®
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Facility:
Name:
City of Hope at Irvine Lennar
Address:
City:
Irvine
Zip:
92618
Country:
United States
Status:
Recruiting
Facility:
Name:
Norton Cancer Institute - MDC
Address:
City:
Louisville
Zip:
40202
Country:
United States
Status:
Recruiting
Facility:
Name:
Duke University; Office of Research Contracts
Address:
City:
Durham
Zip:
27705
Country:
United States
Status:
Recruiting
Facility:
Name:
SCRI Oncology Partners
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
UZ Leuven Gasthuisberg
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Status:
Recruiting
Facility:
Name:
BCCA-Vancouver Cancer Centre
Address:
City:
Vancouver
Zip:
V5Z 4E6
Country:
Canada
Status:
Recruiting
Facility:
Name:
Princess Margaret Cancer Center
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Active, not recruiting
Facility:
Name:
Rigshospitalet; Onkologisk Klinik
Address:
City:
København Ø
Zip:
2100
Country:
Denmark
Status:
Recruiting
Facility:
Name:
CLCC Leon Berard Lyon
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Recruiting
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Recruiting
Facility:
Name:
Clinica Universitaria de Navarra; Servicio de Oncologia
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Status:
Recruiting
Facility:
Name:
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Clinica Universidad de Navarra Madrid; Servicio de Oncología
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Status:
Recruiting
Facility:
Name:
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Status:
Recruiting
Facility:
Name:
Royal Marsden Hospital - Fulham
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
London
Zip:
W1G 6AD
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
The Christie
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Start date:
January 25, 2024
Completion date:
December 15, 2027
Lead sponsor:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
Hoffmann-La Roche
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06004245
