Anti-TIM-3 + Anti-PD-1 Antibodies for Liver Cancer

Recruiting at 1 trial location

Overseen By Jill Drucker, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Hawaii

Must be taking: Antivirals

Must not be taking: PD-1, PD-L1, TIM-3

Disqualifiers: CNS metastases, Active malignancy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 21-day cycles

42 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antiviral therapy for HBV, you must continue it. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Anti-TIM-3 and Anti-PD-1 antibodies for liver cancer?

Research shows that blocking TIM-3, an immune checkpoint, can enhance the body's ability to fight cancer, and combining it with PD-1 inhibitors may improve treatment outcomes. Studies in liver cancer models and other solid tumors suggest that targeting both TIM-3 and PD-1 can potentially overcome resistance to treatment and improve antitumor effects. ^{1 2 3 4 5}

Is the combination of Anti-TIM-3 and Anti-PD-1 antibodies safe for humans?

The research suggests that Anti-TIM-3 antibodies, when used in combination with other treatments like Anti-PD-1 antibodies, might be well-tolerated in experimental models. However, specific safety data for humans is not provided in the available studies. ^{1 3 5 6 7}

How is the drug combination of Anti-TIM-3 and Anti-PD-1 antibodies unique for liver cancer treatment?

This drug combination is unique because it targets two immune checkpoint proteins, TIM-3 and PD-1, which are highly expressed in liver cancer tissues and associated with higher tumor grades. By blocking both proteins, this treatment aims to enhance the immune system's ability to fight cancer and potentially overcome resistance seen with other therapies that target only one checkpoint. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing two drugs, cobolimab and dostarlimab, to help the immune system fight advanced or spreading liver cancer. The drugs work by blocking proteins that allow cancer cells to hide from the immune system, making it easier for the body to attack them.

Research Team

Jared D. Acoba

Principal Investigator

University of Hawaii

Eligibility Criteria

Adults with advanced liver cancer who haven't had systemic therapy can join this trial. They need good kidney function, controlled hepatitis if present, and at least one measurable tumor. They must not have severe lung conditions or be on recent immunosuppressants, live vaccines, or have other active cancers (with some exceptions). Pregnant women are excluded.

Inclusion Criteria

My liver cancer diagnosis was confirmed through lab tests.

My liver disease is mild to moderate.

Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

Exclusion Criteria

I have had an organ or bone marrow transplant.

Psychiatric illness/social situations that would limit compliance with study requirements

I have been treated with drugs targeting PD-1, PD-L1, or TIM-3.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TSR-022 (cobolimab) and TSR-042 (dostarlimab) via IV on day 1, with courses repeating every 21 days in the absence of disease progression or unacceptable toxicity

21-day cycles

1 visit every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 9 weeks

Follow-up visits every 9 weeks

Treatment Details

Interventions

• TSR-022
• TSR-042

Trial Overview The trial is testing the combination of two immune system-boosting drugs: TSR-022 (cobolimab) and TSR-042 (dostarlimab), to see if they help the body fight liver cancer better together than existing treatments.

Participant Groups

Group I: TSR-022 (Cobolimab) and TSR-042 (Dostarlimab) Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Hawaii

Lead Sponsor

Trials

122

Recruited

55,200+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

The TIM-3 monoclonal antibody, LY3321367, demonstrated an acceptable safety profile in a phase Ia/b study with no dose-limiting toxicities observed in 30 patients receiving monotherapy and 28 patients receiving combination therapy.

While LY3321367 showed favorable pharmacokinetics and pharmacodynamics, its antitumor activity was modest, with only 4% objective response rate in combination therapy and 7% in monotherapy for patients previously treated with anti-PD-1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody. Harding, JJ., Moreno, V., Bang, YJ., et al.[2023]

Targeting the Tim-3 inhibitory receptor on T cells may enhance anti-tumor immunity in bladder cancer, especially since many patients do not respond to existing therapies like CTLA-4 and PD-1/PD-L1 blockade.

Tim-3 expression increases with the severity of bladder cancer, suggesting that developing monoclonal antibodies against Tim-3, either alone or with other treatments, could lead to better outcomes for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer. Mohsenzadegan, M., Bavandpour, P., Nowroozi, MR., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Combination therapy with anti-T-cell immunoglobulin and mucin-domain containing molecule 3 and radiation improves antitumor efficacy in murine hepatocellular carcinoma. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Association of TIM-3 with BCLC Stage, Serum PD-L1 Detection, and Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Tumor cell-intrinsic Tim-3 promotes liver cancer via NF-κB/IL-6/STAT3 axis. [2022]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors. [2021]