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

• ClinicalTrials.gov Identifier: NCT03680508
• Recruitment Status: Recruiting
• First Posted: September 21, 2018
• Last Update Posted: October 23, 2023
• Sponsor: University of Hawaii
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): University of Hawaii

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Adult Primary Liver Cancer; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer	Drug: TSR-022 and TSR-042	Phase 2

Detailed 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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of TSR-022 (Cobolimab) in Combination With TSR-042 (Dostarlimab) for the Treatment of Advanced Hepatocellular Carcinoma
• Actual Study Start Date: December 19, 2019
• Estimated Primary Completion Date: October 2024
• Estimated Study Completion Date: October 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: TSR-022 (Cobolimab) and TSR-042 (Dostarlimab); 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; immunotherapy; Other Names: cobolimab, TIM-3 binding antibody; dostarlimab, PD-1 binding antibody

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate [ Time Frame: From date of treatment until the date of best documented response, assessed up to 36 months ]
   Determined by RECIST v1.1 criteria

Secondary Outcome Measures :

1. Objective Response Rate (irRC) [ Time Frame: From date of treatment until the date of best documented response, assessed up to 36 months ]
   Objective response as determined by the immune related Response Criteria
2. Duration of Response [ Time Frame: From date of treatment until the date of progression, assessed up to 36 months ]
   Time from tumor response to progression
3. Time to progression [ Time Frame: From date of treatment until the date of progression, assessed up to 36 months ]
   Time from treatment to progression of cancer
4. Progression free survival [ Time Frame: From date of treatment until the date of progression or death, assessed up to 36 months ]
   Time from treatment to progression of cancer or death
5. Overall survival [ Time Frame: From date of treatment until the date of death, assessed up to 36 months ]
   Time from treatment to death
6. AFP response [ Time Frame: From treatment start to documentation of AFP progression, assessed up to 36 months. ]
   Percentage of AFP decrease from baseline to nadir
7. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0 [ Time Frame: From treatment until cessation of study treatment and resolution of adverse events, assessed up to 36 months ]
   Tabulation of adverse events, CTCAE v4.0

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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
• Female participant has a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential.
• Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.

Exclusion Criteria:

• 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.
• Participant has received a live vaccine within 7 days of initiating protocol therapy.
• Psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant, lactating, breastfeeding, or intending to become pregnant during the study and for 180 days after the study

Contacts and Locations

Contacts

Contact: Jared D Acoba, MD; 8085318521; jacoba@hawaii.edu

Contact: Jill Drucker, MS; 8085643989; IIT@cc.hawaii.edu

Locations

United States, Hawaii

University of Hawaii; Recruiting

Honolulu, Hawaii, United States, 96813

Contact: Jared D Acoba, MD 808-531-8521 jacoba@hawaii.edu

United States, Oregon

Oregon Health & Science University Knight Cancer Institute; Recruiting

Portland, Oregon, United States, 97239

Contact: Adel Kardosh, MD

Sponsors and Collaborators

University of Hawaii

GlaxoSmithKline

Investigators

• Principal Investigator: Jared D Acoba, MD; University of Hawaii

More Information

• Responsible Party: University of Hawaii
• ClinicalTrials.gov Identifier: NCT03680508
• Other Study ID Numbers: ACOBA-2017-2
• First Posted: September 21, 2018
• Last Update Posted: October 23, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Hawaii:

immunotherapy; PD-1; TIM-3

Additional relevant MeSH terms:

Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Dostarlimab; Antibodies; Immunoglobulins; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents