Clinical Trials List
Protocol NumberWP41377
NCT Number(ClinicalTrials.gov Identfier)NCT04338685
2020-05-01 - 2022-12-25
Phase I
Recruiting2
ICD-9155.2
Malignant neoplasm of liver, not specified as primary or secondary
ICD-9156.9
Malignant neoplasm of biliary tract, part unspecified
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
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Trial Applicant
COVANCE TAIWAN SERVICES LIMITED
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Sponsor
F. Hoffmann-La Roche Ltd
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chiun Hsu 無
- 魏以宣 無
- Ying-Chun Shen 無
- TSUNG-HAO LIU 無
- Chih-Hung Hsu 無
- 呂理駿 無
- Ann-Lii Cheng 無
- YU-YUN SHAO 無
- 梁逸歆 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases
Objectives
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.
Test Drug
RO7119929
Active Ingredient
RO7119929
Dosage Form
Capsule
Dosage
1mg, 5mg, 25mg
Endpoints
Primary Outcome Measures :
Nature and Frequency of Dose-Limiting Toxicities [ Time Frame: Baseline up to approximately 14 months ]
Number of Participants with Adverse Events (AEs) According To NCI CTCAE v5.0 [ Time Frame: Baseline up to approximately 14 months ]
Secondary Outcome Measures :
Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Maximum Concentration (Cmax) for RO7117418 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Time of Maximum Concentration Observed (Tmax) for RO7117418 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Area Under the Curve (AUC) for RO7117418 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Half-Life (T1/2) for RO7117418 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Maximum Concentration (Cmax) for RO7117418 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Time of Maximum Concentration Observed (Tmax) for RO7117418 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Area Under the Curve (AUC) for RO7117418 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Half-Life (T1/2) for RO7117418 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Change in Inflammatory PD Biomarker INF-alpha [ Time Frame: Cycle 1 Day 1: Predose, 2, 6, 12h postdose; Cycle 2 Day 2: Predose, 2, 6 h postdose; Cycles 1 and 2 Day 2: 24, 30h postdose ]
Change in Inflammatory PD Biomarker ISGs [ Time Frame: Cycle 1 Day 1: Predose, 2, 6, 12h postdose; Cycle 2 Day 2: Predose, 2, 6h postdose; Cycles 1 and 2 Day 2: 24, 30h postdose ]
Objective Response Rate (ORR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
Disease Control Rate (DCR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
Duration of Response (DOR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
Progression-Free Survival (PFS) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
Overall Survival (OS) [ Time Frame: Baseline up to approximately 14 months ]
Nature and Frequency of Dose-Limiting Toxicities [ Time Frame: Baseline up to approximately 14 months ]
Number of Participants with Adverse Events (AEs) According To NCI CTCAE v5.0 [ Time Frame: Baseline up to approximately 14 months ]
Secondary Outcome Measures :
Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Maximum Concentration (Cmax) for RO7117418 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Time of Maximum Concentration Observed (Tmax) for RO7117418 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Area Under the Curve (AUC) for RO7117418 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Half-Life (T1/2) for RO7117418 Following Administration of RO7119929 [ Time Frame: Cycle 1, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycles 1 and 2, Day 2: 24, 30h postdose ]
Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Maximum Concentration (Cmax) for RO7117418 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Time of Maximum Concentration Observed (Tmax) for RO7117418 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Area Under the Curve (AUC) for RO7117418 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Half-Life (T1/2) for RO7117418 Following Administration of RO7119929 in Fasting Conditions [ Time Frame: Cycle 2, Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12h postdose; Cycle 2, Day 2: 24, 30h postdose ]
Change in Inflammatory PD Biomarker INF-alpha [ Time Frame: Cycle 1 Day 1: Predose, 2, 6, 12h postdose; Cycle 2 Day 2: Predose, 2, 6 h postdose; Cycles 1 and 2 Day 2: 24, 30h postdose ]
Change in Inflammatory PD Biomarker ISGs [ Time Frame: Cycle 1 Day 1: Predose, 2, 6, 12h postdose; Cycle 2 Day 2: Predose, 2, 6h postdose; Cycles 1 and 2 Day 2: 24, 30h postdose ]
Objective Response Rate (ORR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
Disease Control Rate (DCR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
Duration of Response (DOR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
Progression-Free Survival (PFS) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
Overall Survival (OS) [ Time Frame: Baseline up to approximately 14 months ]
Inclution Criteria
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 B7 or better
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 B7 or better
Exclusion Criteria
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 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 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 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.
The Estimated Number of Participants
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Taiwan
20 participants
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Global
100 participants
