- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04338685
A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases
December 4, 2023 updated by: Hoffmann-La Roche
A First In Human, Open Label, Dose Escalation Phase I Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Clinical Activity Profile Of Single Agent RO7119929 (TLR7 Agonist) Administered Orally To Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases
Phase I study of RO7119929 given orally to participants with unresectable advanced or metastatic primary liver cancers and other solid tumors with predominant liver involvement.
The primary objective of the study is to explore the safety and to determine the maximum tolerated dose (MTD) and/or optimal biologic dose (OBD) of RO7119929 as single agent.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
55
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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København Ø, Denmark, 2100
- Rigshospitalet; Onkologisk Klinik
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Hong Kong, Hong Kong
- Queen Mary Hospital; Dept of Medicine
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Seoul, Korea, Republic of, 03080
- Seoul National University Hospital
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Seoul, Korea, Republic of, 05505
- Asan Medical Center
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Barcelona, Spain, 08035
- Hospital Universitari Vall d'Hebron; Oncology
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Madrid, Spain, 28027
- Clinica Universidad de Navarra Madrid; Servicio de Oncología
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Navarra
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Pamplona, Navarra, Spain, 31620
- Clinica Universidad de Navarra
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Taipei, Taiwan, 11490
- Tri-Service General Hospital
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Taipei City, Taiwan, 10041
- National Taiwan Uni Hospital
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California
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Duarte, California, United States, 91010
- City of Hope Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Histologically confirmed diagnosis of one of the following: unresectable advanced or metastatic HCC (including fibrolamellar HCC) not amenable to a curative treatment approach, unresectable advanced or metastatic intrahepatic or perihilar (Klatskin) BTC not amenable to a curative treatment approach, extrahepatic BTC or gallbladder cancer infiltrating the liver or metastasized into the liver with predominant liver disease, not amenable to a curative treatment approach, metastasized colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), Gastric cancer (GC), renal cell carcinoma (RCC), triple negative breast cancer (TNBC), cutaneous melanoma, or ocular melanoma with predominant liver disease not amenable to a curative treatment approach. Participants with other solid tumors with predominant liver disease not amenable to a curative treatment approach might be enrolled after Sponsor approval
- Measurable disease with at least one measurable locally untreated liver lesion, as defined by RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate hematologic and major organ functions
- Participants for which there is no available standard therapy likely to confer clinical benefit, or participants who are not candidates for such available therapy
- Life expectancy of ≥12 weeks, approximated with Royal Marsden Hospital score 0-1 or Gustave Roussy Immune (GRIm) score 0-1. Participants with a Royal Marsden Hospital or GRIm score of ≥2 and a life expectancy of ≥12 weeks according to the investigator's clinical judgement may be enrolled after Medical Monitor approval has been obtained.
- For participants with HCC: Child-Pugh score of A6 or better
Exclusion Criteria:
- History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days prior to Screening
- Evidence of any extra-hepatic primary tumor or metastasis requiring prompt medical intervention
- Receipt of prior therapy with a TLR7/8/9 agonist and/or IFN-alpha
- Prior chemotherapy, antibody, or other registered or experimental cancer treatment within 3 weeks of study Cycle 1 Day 1. Specifically, no CPI antibody is allowed to be administered within 6 weeks of study Cycle 1 Day 1
- Receipt of investigational agent for any other indication within 3 weeks of dosing
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
- Local therapy to liver (e.g. radiofrequency ablation, percutaneuous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, and transarterial embolization) within 3 weeks prior to initiation of study treatment, radioembolization within 3 months prior to initiation of study treatment, or non-recovery from side effects of such procedure
- Treatment-related toxicities from prior cancer therapy that have not resolved to </= Grade 1 CTC AE prior to study treatment with the exception of the following Grade 2 toxicities:
alopecia, peripheral neuropathy, any laboratory changes that still lie within the inclusion criteria defined above
- History of other malignancy within 2 years; exception for ductal carcinoma in situ not requiring chemotherapy, low grade cervical intraepithelial neoplasia (CIN), nonmelanoma skin cancer, low grade localized prostate cancer (Gleason score < Grade 7), or optimally treated Stage 1 uterine cancer.
- Active or history of immunologic-mediated disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren's syndrome or Guillain-Barré syndrome
- Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection.
- Ascites, pleural effusion, or pericardial effusion requiring medical intervention within 12 months prior to study entry.
- History of human immunodeficiency virus (HIV) infection
- Active hepatitis B virus (HBV) infection
- Coinfection of HBV and hepatitis C virus (HCV).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Part A1-1 mg RO7119929
Participants received 1mg RO7119929 every week in 3-week cycles.
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RO7119929 will be administered orally as a capsule
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Experimental: Part A1-3 mg RO7119929
Participants received 4 mg RO7119929 every week in 3-week cycles
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RO7119929 will be administered orally as a capsule
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Experimental: Part A1 - 6 mg RO7119929
Participants received 6 mg RO7119929 every week in 3-week cycles
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RO7119929 will be administered orally as a capsule
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Experimental: Part A1 -9 mg RO7119929
Participants received 9 mg RO7119929 every week in 3-week cycles
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RO7119929 will be administered orally as a capsule
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Experimental: Part B1-5 mg RO7119929
Participants with both available and evaluable tumor biopsy samples received 5 mg RO7119929 on Cycle 1 Day 1 to month 12
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RO7119929 will be administered orally as a capsule
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Experimental: Part A2- 2/5/5 mg RO7119929
Participants received RO7119929 QW with step-up dosing of 2/5/5 mg during Cycle 1.
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RO7119929 will be administered orally as a capsule
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Experimental: Part A2- 2/5/6 mg RO7119929
Participants received RO7119929 QW with step-up dosing of 2/5/6 mg during Cycle 1.
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RO7119929 will be administered orally as a capsule
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Experimental: Part A3-4 mg RO7119929
Participants received tocilizumab pre-treatment on Cycle 1 Day 1, approximately 2 hours prior to RO7119929 administration and 4 mg RO7119929 every week in 3-week cycles
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Tocilizumab will be administered in case of severe steroid-refractory cytokine release syndrome. Tocilizumab will be administered as concentrate for solution for IV infusion at a dose: for participants > 30 kg: 8 mg/kg, for participants < 30 kg: 12mg/kg IV
Other Names:
RO7119929 will be administered orally as a capsule
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Nature and Frequency of Dose-Limiting Toxicities
Time Frame: Baseline up to approximately 14 months
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Baseline up to approximately 14 months
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Number of Participants with Adverse Events (AEs) According To NCI CTCAE v5.0
Time Frame: Baseline up to approximately 14 months
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Baseline up to approximately 14 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Objective Response Rate (ORR) according to RECIST v1.1
Time Frame: Baseline up to approximately 14 months
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Baseline up to approximately 14 months
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Disease Control Rate (DCR) according to RECIST v1.1
Time Frame: Baseline up to approximately 14 months
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Baseline up to approximately 14 months
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Progression-Free Survival (PFS) according to RECIST v1.1
Time Frame: Baseline up to approximately 14 months
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Baseline up to approximately 14 months
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Overall Survival (OS)
Time Frame: Baseline up to approximately 14 months
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Baseline up to approximately 14 months
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Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929
Time Frame: Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
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Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
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Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929
Time Frame: Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
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Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
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Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929
Time Frame: Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
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Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
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Half-Life (T1/2) for RO7119929 Following Administration of RO7119929
Time Frame: Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
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Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 16, 2020
Primary Completion (Actual)
January 9, 2023
Study Completion (Actual)
January 9, 2023
Study Registration Dates
First Submitted
April 6, 2020
First Submitted That Met QC Criteria
April 6, 2020
First Posted (Actual)
April 8, 2020
Study Record Updates
Last Update Posted (Estimated)
December 6, 2023
Last Update Submitted That Met QC Criteria
December 4, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Neoplastic Processes
- Biliary Tract Diseases
- Carcinoma
- Carcinoma, Hepatocellular
- Neoplasm Metastasis
- Biliary Tract Neoplasms
Other Study ID Numbers
- WP41377
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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