Brief Title
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
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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Nature and Frequency of Dose-Limiting Toxicities
Secondary Outcome
Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929
Condition
Carcinoma, Hepatocellular
Intervention
RO7119929
Study Arms / Comparison Groups
RO7119929
Description: 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).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
55
Start Date
July 16, 2020
Completion Date
June 30, 2023
Primary Completion Date
December 31, 2022
Eligibility 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 Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Clinical Trials, ,
Location Countries
Denmark
Location Countries
Denmark
Administrative Informations
NCT ID
NCT04338685
Organization ID
WP41377
Responsible Party
Sponsor
Study Sponsor
Hoffmann-La Roche
Study Sponsor
Clinical Trials, Study Director, Hoffmann-La Roche
Verification Date
June 2022