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

NCT04338685 | Completed Phase 1 Results FDA Drug

• 1 other identifier: WP41377
• Study Type: interventional
• Target: 55
• Locations: 6 countries
• Sites: 10

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.

Conditions

Carcinoma, Hepatocellular; Biliary Tract Cancer; Secondary Liver Cancer; Liver Metastases

Keywords

TLR7 Agonist

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-Limiting Toxicities (DLT)

  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.

  Baseline up to approximately 14 months

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

  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.

  Baseline up to approximately 14 months

Secondary Outcomes (11)

• Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929

  Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)

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

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

• Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929

  Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)

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

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

• Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929

  Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)

Study Arms (8)

Part A1-1 mg RO7119929

EXPERIMENTAL

Participants received 1mg RO7119929 every week in 3-week cycles.

Drug: RO7119929

Part A1-3 mg RO7119929

EXPERIMENTAL

Participants received 4 mg RO7119929 every week in 3-week cycles

Drug: RO7119929

Part A1 - 6 mg RO7119929

EXPERIMENTAL

Participants received 6 mg RO7119929 every week in 3-week cycles

Drug: RO7119929

Part A1 -9 mg RO7119929

EXPERIMENTAL

Participants received 9 mg RO7119929 every week in 3-week cycles

Drug: RO7119929

Part B1-5 mg RO7119929

EXPERIMENTAL

Participants with both available and evaluable tumor biopsy samples received 5 mg RO7119929 on Cycle 1 Day 1 to month 12

Drug: RO7119929

Part A2- 2/5/5 mg RO7119929

EXPERIMENTAL

Participants received RO7119929 QW with step-up dosing of 2/5/5 mg during Cycle 1.

Drug: RO7119929

Part A2- 2/5/6 mg RO7119929

EXPERIMENTAL

Participants received RO7119929 QW with step-up dosing of 2/5/6 mg during Cycle 1.

Drug: RO7119929

Part A3-4 mg RO7119929

EXPERIMENTAL

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

Drug: RO7119929; Drug: Tocilizumab

Interventions

RO7119929 DRUG

RO7119929 will be administered orally as a capsule

Part A1 - 6 mg RO7119929; Part A1 -9 mg RO7119929; Part A1-1 mg RO7119929; Part A1-3 mg RO7119929; Part A2- 2/5/5 mg RO7119929; Part A2- 2/5/6 mg RO7119929; Part A3-4 mg RO7119929; Part B1-5 mg RO7119929

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

Also known as: Actemra

Part A3-4 mg RO7119929

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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).

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (10)

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Queen Mary Hospital; Dept of Medicine

Hong Kong, Hong Kong

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31620, Spain

Location

Hospital Universitari Vall d'Hebron; Oncology

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra Madrid; Servicio de Oncología

Madrid, 28027, Spain

Location

National Taiwan Uni Hospital

Taipei, 10041, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Biliary Tract Neoplasms

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Biliary Tract Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, multi-center, single-arm, multiple-ascending dose escalation

Study Record Dates

• First Submitted: April 6, 2020
• First Posted: April 8, 2020
• Study Start: July 16, 2020
• Primary Completion: January 9, 2023
• Study Completion: January 9, 2023
• Last Updated: December 9, 2024
• Results First Posted: December 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); HK (1); US (1); DK (1); KR (2); TW (2)