Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04338685
Recruitment Status : Recruiting
First Posted : April 8, 2020
Last Update Posted : June 9, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Biliary Tract Cancer Secondary Liver Cancer Liver Metastases Drug: RO7119929 Drug: Tocilizumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open label, multi-center, single-arm, multiple-ascending dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 16, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Tocilizumab

Arm Intervention/treatment
Experimental: RO7119929
Participants will receive RO7119929 every week in 3-week cycles. In Part A (dose-escalation on a weekly schedule) maximum tolerated dose (MTD) and/or recommended dose for expansion cohorts (RDE) will be determined. Following determination of MTD and/or RDE, treatment will commence at up to three different doses in specific expansion cohorts of participants for extended PD analysis (Part B).
Drug: RO7119929
RO7119929 will be administered orally as a capsule at starting dose 1 mg on weekly (QW) dosing regimen

Drug: Tocilizumab

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 Name: Actemra




Primary Outcome Measures :
  1. Nature and Frequency of Dose-Limiting Toxicities [ Time Frame: Baseline up to approximately 14 months ]
  2. Number of Participants with Adverse Events (AEs) According To NCI CTCAE v5.0 [ Time Frame: Baseline up to approximately 14 months ]

Secondary Outcome Measures :
  1. 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 1, Day 15: Predose, 2, 8h 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 (cycle length = 21 days) ]
  2. 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 1, Day 15: Predose, 2, 8h 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 (cycle length = 21 days) ]
  3. 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 1, Day 15: Predose, 2, 8h 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 (cycle length = 21 days) ]
  4. 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 1, Day 15: Predose, 2, 8h 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 (cycle length = 21 days) ]
  5. 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 1, Day 15: Predose, 2, 8h 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 (cycle length = 21 days) ]
  6. 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 1, Day 15: Predose, 2, 8h 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 (cycle length = 21 days) ]
  7. 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 1, Day 15: Predose, 2, 8h 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 (cycle length = 21 days) ]
  8. 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 1, Day 15: Predose, 2, 8h 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 (cycle length = 21 days) ]
  9. 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 (cycle length = 21 days) ]
  10. 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 (cycle length = 21 days) ]
  11. 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 (cycle length = 21 days) ]
  12. 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 (cycle length = 21 days) ]
  13. 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 (cycle length = 21 days) ]
  14. 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 (cycle length = 21 days) ]
  15. 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 (cycle length = 21 days) ]
  16. 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 (cycle length = 21 days) ]
  17. 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 (cycle length = 21 days) ]
  18. 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 (cycle length = 21 days) ]
  19. Objective Response Rate (ORR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
  20. Disease Control Rate (DCR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
  21. Duration of Response (DOR) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
  22. Progression-Free Survival (PFS) according to RECIST v1.1 [ Time Frame: Baseline up to approximately 14 months ]
  23. Overall Survival (OS) [ Time Frame: Baseline up to approximately 14 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04338685


Contacts
Layout table for location contacts
Contact: Reference Study ID Number www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
Layout table for location information
United States, California
City of Hope Cancer Center Not yet recruiting
Duarte, California, United States, 91010
Keck School of Medicine - University of Southern California Not yet recruiting
Los Angeles, California, United States, 90033
United States, District of Columbia
Georgetown University Not yet recruiting
Washington, District of Columbia, United States, 20007
Canada, Ontario
Princess Margaret Cancer Center Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Denmark
Rigshospitalet; Onkologisk Klinik Recruiting
København Ø, Denmark, 2100
Hong Kong
Queen Mary Hospital; Dept of Medicine Not yet recruiting
Hong Kong, Hong Kong
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Spain
Clínica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31620
Hospital Universitari Vall d'Hebron; Oncology Recruiting
Barcelona, Spain, 08035
Institut Català d'Oncologia (ICO) d'Hospitalet Not yet recruiting
Barcelona, Spain, 08908
Clinica Universidad de Navarra Madrid; Servicio de Oncología Active, not recruiting
Madrid, Spain, 28027
START Madrid. Centro Integral Oncologico Clara Campal; Unidad de Fase I-Oncologica Not yet recruiting
Madrid, Spain, 28050
Hospital Clínico Universitario de Valencia; Medical Oncology Not yet recruiting
Valencia, Spain, 46010
Taiwan
National Taiwan Uni Hospital Recruiting
Taipei City, Taiwan, 10041
Tri-Service General Hospital Recruiting
Taipei, Taiwan, 11490
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04338685    
Other Study ID Numbers: WP41377
First Posted: April 8, 2020    Key Record Dates
Last Update Posted: June 9, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Hoffmann-La Roche:
TLR7 Agonist
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Neoplasm Metastasis
Carcinoma, Hepatocellular
Biliary Tract Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplastic Processes
Pathologic Processes
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Biliary Tract Diseases