Recruitment

Recruitment Status
Recruiting

Inclusion Criteria

Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
Subjects with HBV infection are required to be receiving effective antiviral therapy and have a viral load less than 100 IU/mL. Antiviral therapy is not required for subjects with HCV infection
Barcelona Clinic Liver Cancer Stage B or C
...
Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
Subjects with HBV infection are required to be receiving effective antiviral therapy and have a viral load less than 100 IU/mL. Antiviral therapy is not required for subjects with HCV infection
Barcelona Clinic Liver Cancer Stage B or C
No prior systemic therapy for HCC
ECOG performance status 0-1
Cirrhosis grade of Child-Pugh class A or B7
Age ≥ 18 years
Histologically or cytologically confirmed hepatocellular cancer
Have at least one tumor lesion that can be accurately measured according to Response Evaluation Criteria in Solid Tumor (RECIST v1.1)
Prior local therapy, such as surgery, radioembolization, chemoembolization, or radiofrequency ablation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment
Have adequate hematologic and renal function
Resolved acute effects of any prior therapy to baseline or Grade ≤1 NCI CTCAE

Exclusion Criteria

Known history of Human Immunodeficiency Virus (HIV) infection
Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
Psychiatric illness/social situations that would limit compliance with study requirements
...
Known history of Human Immunodeficiency Virus (HIV) infection
Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
Psychiatric illness/social situations that would limit compliance with study requirements
Active or untreated central nervous system (CNS) and leptomeningeal metastases are excluded
Participant must not have a known hypersensitivity to TSR-042 and TSR-022 components or excipients.
History of organ transplantation including allogeneic bone marrow transplantation
Participants with active malignancy (other than HCC) or a prior malignancy within the past 2 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible
History of idiopathic pulmonary fibrosis, interstitial lung disease, bronchial asthma, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis
Participant must not have serious, uncontrolled medical disorder, or nonmalignant systemic disease. Examples include, but are not limited to uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome.
Participant has a diagnosis of immunodeficiency or has receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
Participant must not be simultaneously enrolled in any interventional clinical trial
Prior therapy with any medication targeting PD-1, PD-L1, or TIM-3
Pregnant, lactating, breastfeeding, or intending to become pregnant during the study and for 180 days after the study
Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (.ie., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Participants must not have received investigational therapy ≤4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior to initiating protocol therapy.

Summary

Conditions
  • Adult Primary Liver Cancer
  • Advanced Adult Primary Liver Cancer
  • Localized Unresectable Adult Primary Liver Cancer
Type
Interventional
Phase
Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

PRIMARY OBJECTIVES: I. To assess the objective response rate (ORR) as determined by RECIST v1.1 of advanced hepatocellular cancer (HCC) patients treated with TSR-022 (cobolimab, TIM-3 binding antibody) and TSR-042 (dostarlimab, PD-1 binding antibody). SECONDARY OBJECTIVES: I. To determine the ORR as...

PRIMARY OBJECTIVES: I. To assess the objective response rate (ORR) as determined by RECIST v1.1 of advanced hepatocellular cancer (HCC) patients treated with TSR-022 (cobolimab, TIM-3 binding antibody) and TSR-042 (dostarlimab, PD-1 binding antibody). SECONDARY OBJECTIVES: I. To determine the ORR as determined by the immune related Response Criteria (irRC), duration of response (DOR), time to progression (TTP), progression free survival (PFS), overall survival (OS), and alpha-fetoprotein (AFP) response of study participants. II. To evaluate the safety profile of treated patients. OUTLINE: Patients receive TSR-022 (cobolimab, TIM-3 binding antibody) and TSR-042 (dostarlimab, PD-1 binding antibody) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 9 weeks.

Inclusion Criteria

Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
Subjects with HBV infection are required to be receiving effective antiviral therapy and have a viral load less than 100 IU/mL. Antiviral therapy is not required for subjects with HCV infection
Barcelona Clinic Liver Cancer Stage B or C
...
Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
Subjects with HBV infection are required to be receiving effective antiviral therapy and have a viral load less than 100 IU/mL. Antiviral therapy is not required for subjects with HCV infection
Barcelona Clinic Liver Cancer Stage B or C
No prior systemic therapy for HCC
ECOG performance status 0-1
Cirrhosis grade of Child-Pugh class A or B7
Age ≥ 18 years
Histologically or cytologically confirmed hepatocellular cancer
Have at least one tumor lesion that can be accurately measured according to Response Evaluation Criteria in Solid Tumor (RECIST v1.1)
Prior local therapy, such as surgery, radioembolization, chemoembolization, or radiofrequency ablation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment
Have adequate hematologic and renal function
Resolved acute effects of any prior therapy to baseline or Grade ≤1 NCI CTCAE

Exclusion Criteria

Known history of Human Immunodeficiency Virus (HIV) infection
Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
Psychiatric illness/social situations that would limit compliance with study requirements
...
Known history of Human Immunodeficiency Virus (HIV) infection
Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
Psychiatric illness/social situations that would limit compliance with study requirements
Active or untreated central nervous system (CNS) and leptomeningeal metastases are excluded
Participant must not have a known hypersensitivity to TSR-042 and TSR-022 components or excipients.
History of organ transplantation including allogeneic bone marrow transplantation
Participants with active malignancy (other than HCC) or a prior malignancy within the past 2 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible
History of idiopathic pulmonary fibrosis, interstitial lung disease, bronchial asthma, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis
Participant must not have serious, uncontrolled medical disorder, or nonmalignant systemic disease. Examples include, but are not limited to uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome.
Participant has a diagnosis of immunodeficiency or has receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
Participant must not be simultaneously enrolled in any interventional clinical trial
Prior therapy with any medication targeting PD-1, PD-L1, or TIM-3
Pregnant, lactating, breastfeeding, or intending to become pregnant during the study and for 180 days after the study
Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (.ie., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Participants must not have received investigational therapy ≤4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior to initiating protocol therapy.

Locations

Honolulu, Hawaii, 96813
Honolulu, Hawaii, 96813

Tracking Information

NCT #
NCT03680508
Collaborators
GlaxoSmithKline
Investigators
  • Principal Investigator: Jared D Acoba, MD University of Hawaii
  • Jared D Acoba, MD University of Hawaii