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Completed

NCT Number: 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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Rigshospitalet; Onkologisk Klinik, København Ø, Denmark

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

RO7119929

Drug

RO7119929 will be administered orally as a capsule

Tocilizumab

Drug

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: Actemra

Primary outcomes

  1. Number of Participants With Dose-Limiting Toxicities (DLT)

    Time frame: Baseline up to approximately 14 months

    A DLT is defined as a clinically significant AE (classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.5.0) or significant laboratory abnormality 1) occurring during an assessment period of 21 days or 28 days after first dose of study treatment, respectively, and 2) is not attributed to disease progression, concomitant illness or another clearly identifiable cause.

  2. Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0

    Time frame: Baseline up to approximately 14 months

    An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Secondary outcomes

  1. 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)

  2. Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose

    Time frame: Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)

  3. 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)

  4. Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose

    Time frame: Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)

  5. 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)

  6. Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose

    Time frame: Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)

  7. 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)

  8. Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose

    Time frame: Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)

  9. Progression-Free Survival (PFS) According to RECIST v1.1

    Time frame: Baseline up to approximately 14 months

    Progression-free survival (PFS) is defined as the time from randomization to disease progression or death from any cause.

  10. Objective Response Rate (ORR) According to RECIST v1.1

    Time frame: Baseline up to approximately 14 months

    ORR is defined as the number of patients who achieve a response, which can either be complete response (complete disappearance of lesions) or partial response (reduction in the sum of maximal tumor diameters by at least 30% or more).

  11. Overall Survival (OS)

    Time frame: Baseline up to approximately 14 months

    Overall survival (OS) is defined as the time from randomization to death

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Apr 8, 2020
Registry last updated
Dec 9, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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