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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if two experimental drugs, TSR-022 (Cobolimab, an anti-TIM-3 antibody) and TSR-042 (Dostarlimab, an anti-PD-1 antibody), can help the immune system combat liver cancer. These drugs may stop tumor growth and enable the body's natural defenses to attack the cancer. The trial targets individuals with advanced liver cancer who have not yet received treatment. Those with advanced liver cancer confirmed by a doctor might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of TSR-022 (cobolimab) and TSR-042 (dostarlimab) is generally safe for patients. In studies involving patients with non–small cell lung cancer, this treatment proved safe at various dose levels. While some side effects occurred, they were manageable. This combination is now being tested for liver cancer, presenting a different context. The current trial phase suggests some existing safety evidence, but researchers continue to gather more data to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver cancer because they target specific immune checkpoints, offering a new approach compared to traditional therapies. Unlike conventional treatments like chemotherapy, TSR-022 (cobolimab) and TSR-042 (dostarlimab) work by blocking TIM-3 and PD-1 pathways, respectively. This mechanism is designed to enhance the body's immune response against cancer cells, potentially leading to better outcomes. This innovative strategy could offer new hope for patients who have limited options with existing treatments.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Participants in this trial will receive a combination of TSR-022 (cobolimab) and TSR-042 (dostarlimab). Research has shown that this combination can help the immune system fight cancer cells. Studies have found it effective and safe for patients with advanced non-small cell lung cancer, and it may benefit other cancer types as well. Early results suggest these drugs can shrink tumors in liver cancer patients. By targeting specific proteins, TIM-3 and PD-1, they help the immune system recognize and attack cancer cells. This approach has shown initial success, offering hope for those with liver cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Jared D. Acoba

Principal Investigator

University of Hawaii

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03680508

NCT03680508 | TSR-022 (anti-TIM-3 Antibody) and ... 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 ...

2. onclive.com onclive.com/view/cobolimab-dostarlimab-combination-shows-initial-efficacy-and-safety-signals-in-advanced-nsclc

Cobolimab/Dostarlimab Combination Shows Initial Efficacy ... Cobolimab plus dostarlimab-gxly showed activity and acceptable safety across all dose levels assessed in patients with non–small cell lung cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03680508?term=NCT03680508&intr=NCT03680508&rank=1

TSR-022 (anti-TIM-3 Antibody) and TSR-042 (anti-PD-1 ... 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 ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-02774

Cobolimab and Dostarlimab for the Treatment of BCLC ... This phase II trial tests whether cobolimab and dostarlimab work to shrink tumors in patients with BCLC stage B or C liver cancer.

5. trials.ohsu.edu trials.ohsu.edu/s/experimental-drugs-called-cobolimab-tsr-022-and-dostarlimab-tsr-042-for-the-treatment-of-advanced-hepatocellular-carcinoma-838179/

Experimental Drugs called Cobolimab (TSR-022) and ... This study is a phase ll and the purpose of this study is to determine if giving TSR-022 and TSR-042 will shrink the tumor in participants with hepatocellular ...

6. clinicaltrialsarena.com clinicaltrialsarena.com/news/gsk-anti-tim-3-antibody-fails-in-phase-iii-nsclc-trial/

GSK's anti-TIM-3 antibody fails in Phase III NSCLC trial GSK's anti-TIM-3 antibody fails in Phase III NSCLC trial. GSK is also investigating cobolimab in Phase II studies in liver cancer, cervical ...