TSR-022 (Anti-TIM-3 Antibody) and TSR-042 (Anti-PD-1 Antibody) in Patients With Liver Cancer

NCT03680508 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ACOBA-2017-2
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

TSR-022 (cobolimab, TIM-3 binding antibody) and TSR-042 (dostarlimab, PD-1 binding antibody) may stop the growth of tumor cells by allowing the immune system to attack the cancer. This phase II trial is studying how well TSR-022 (cobolimab, TIM-3 binding antibody) and TSR-042 (dostarlimab, PD-1 binding antibody) work in combination in treating patients with locally advanced or metastatic liver cancer.

Conditions

Localized Unresectable Adult Primary Liver Cancer; Adult Primary Liver Cancer; Advanced Adult Primary Liver Cancer

Keywords

immunotherapy; PD-1; TIM-3

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Determined by RECIST v1.1 criteria

  From date of treatment until the date of best documented response, assessed up to 36 months

Secondary Outcomes (7)

• Objective Response Rate (irRC)

  From date of treatment until the date of best documented response, assessed up to 36 months

• Duration of Response

  From date of treatment until the date of progression, assessed up to 36 months

• Time to progression

  From date of treatment until the date of progression, assessed up to 36 months

• Progression free survival

  From date of treatment until the date of progression or death, assessed up to 36 months

• Overall survival

  From date of treatment until the date of death, assessed up to 36 months

Study Arms (1)

TSR-022 (Cobolimab) and TSR-042 (Dostarlimab)

EXPERIMENTAL

Patients receive TSR-022 (cobolimab, TIM-3 binding antibody) and TSR-042 (dostarlimab, PD-1 binding antibody) via IV day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: TSR-022 and TSR-042

Interventions

TSR-022 and TSR-042 DRUG

immunotherapy

Also known as: cobolimab, TIM-3 binding antibody, dostarlimab, PD-1 binding antibody

TSR-022 (Cobolimab) and TSR-042 (Dostarlimab)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed hepatocellular cancer
• Barcelona Clinic Liver Cancer Stage B or C
• Cirrhosis grade of Child-Pugh class A or B7
• 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
• Have at least one tumor lesion that can be accurately measured according to Response Evaluation Criteria in Solid Tumor (RECIST v1.1)
• No prior systemic therapy for HCC
• Age ≥ 18 years
• ECOG performance status 0-1
• Resolved acute effects of any prior therapy to baseline or Grade ≤1 NCI CTCAE
• Have adequate hematologic function as documented by ANC ≥ 1000/μcl, platelet count ≥ 60,000/μcl, and hemoglobin ≥ 8.5 mg/dl
• Have adequate renal function as determined by a measured or calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault formula
• Have adequate hepatic function, as documented by ALT and AST ≤5x upper limit of normal, total bilirubin ≤3 mg/dL, and albumin ≥2.8 g/dL
• International normalized ratio (INR) or prothrombin time (PT) ≤2× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants
• 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
• Participants must agree to not donate blood during the study or for 90 days after the last dose of protocol therapy

You may not qualify if:

• Participant must not be simultaneously enrolled in any interventional clinical trial
• Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
• 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.
• Active or untreated central nervous system (CNS) and leptomeningeal metastases are excluded
• Prior therapy with any medication targeting PD-1, PD-L1, or TIM-3
• Participant must not have a known hypersensitivity to TSR-042 and TSR-022 components or excipients.
• 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
• 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.
• Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure New York Heart Association Class II or higher
• Known history of Human Immunodeficiency Virus (HIV) infection
• Active tuberculosis infection or other microbial infection or any active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
• 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.
• History of idiopathic pulmonary fibrosis, interstitial lung disease, bronchial asthma, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis
• History of organ transplantation including allogeneic bone marrow transplantation
• 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.

Sponsors & Collaborators

• University of Hawaii: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

dostarlimab

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

Study Officials

• Jared D Acoba, MD

  University of Hawaii

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 21, 2018
• Study Start: December 19, 2019
• Primary Completion: March 6, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)