Tislelizumab for Liver Cancer

Recruiting at 1 trial location

Overseen By Salma Jabbour, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must be taking: Suppressive therapy

Must not be taking: Immunotherapy, Corticosteroids, Antibiotics, others

Disqualifiers: HIV, Immunodeficiency, Metastases, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

35 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 certain treatments like immunotherapy or herbal medicines for cancer, you may need to stop those before starting the trial.

What data supports the effectiveness of the drug Tislelizumab for liver cancer?

Tislelizumab has shown promising results in treating liver cancer, particularly hepatocellular carcinoma (HCC), by demonstrating antitumor activity and a tolerable safety profile in clinical trials. It has been effective as a second-line treatment for HCC and is being compared to sorafenib, another drug, as a first-line treatment for advanced cases. ^{1 2 3 4 5}

Is Tislelizumab safe for humans?

Tislelizumab has been shown to have an acceptable safety profile in clinical studies for various cancers, including liver cancer. Common side effects include tiredness, low red blood cell count (anemia), and low white blood cell count (neutrophils), while serious risks involve respiratory infections or liver damage. ^{1 2 3 4 6}

How is the drug Tislelizumab unique for treating liver cancer?

Tislelizumab is unique because it is a modified antibody that targets the PD-1 protein, which helps the immune system attack cancer cells more effectively. It has shown promise in treating liver cancer by potentially offering a more tolerable safety profile and economic advantage compared to other similar drugs. ^{1 3 4 5 7}

What is the purpose of this trial?

The investigators hypothesize that the addition of Tislelizumab after definitive local therapy for locally advanced inoperable Hepatocellular carcinoma (HCC) will synergize with local therapy as well as treat micro metastatic disease and improve one year progression-free survival rates for participants and optimize local control.

Research Team

Salma Jabbour, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for adults with advanced inoperable liver cancer (HCC) who haven't had systemic therapy but may have had TACE. They should be treatment-ready, without severe liver impairment (Child-Pugh A or B7), and no spread of cancer outside the liver. Participants need good organ function, manageable pain levels, a life expectancy over six months, and must agree to use effective birth control.

Inclusion Criteria

Demonstrate adequate bone marrow and organ function as defined below: Hematologic - Absolute neutrophil count (ANC) ≥ 1,500/mcL, Hemoglobin > 8.5 g/dL, Platelet count ≥ 75,000/mcL; Renal - Serum creatinine OR calculated* serum creatinine clearance (GFR can be used in place of creatinine or creatinine clearance) ≤ 1.5x upper limit of normal (ULN) OR ≥ 30 mL/min for participants with creatinine levels > 1.5x institutional ULN; Urine protein Urine dipstick for proteinuria < 2+ within 7 days prior to start of study treatment *Participants with ≥ 2+ proteinuria on dipstick analysis at baseline should undergo a 24-hour urine collection which must demonstrate < 1g of protein in 24 hours; Hepatic - Serum total bilirubin ≤ 3 mg/dL, AST (SGOT) and ALT (SGPT) ≤ 5x ULN, Alkaline phosphatase (ALP) ≤ 8x ULN Coagulation - International Normalized Ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 2.0x ULN *This applies only to participants not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation should be on a stable dose

Written informed consent

Must have 1 target lesion measurable in 1 dimension according to RECIST 1.1

Exclusion Criteria

I have had recent serious heart or stroke issues.

I have a skin condition like eczema or psoriasis, but it affects less than 10% of my body and is well-controlled with mild creams.

Participants with clinically meaningful encephalopathy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Local Therapy

Participants receive local therapy including TACE+ RT or Ablation + RT or RT alone

4-6 weeks

2-3 visits (in-person)

Tislelizumab Treatment

Participants receive Tislelizumab before and after radiation therapy

48 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

Regular follow-up visits

Treatment Details

Interventions

• Tislelizumab

Trial Overview The study tests if Tislelizumab can improve survival rates when given after local treatments like radiation for HCC. It aims to see if this drug helps control the disease locally and fights off tiny undetected spreads of cancer.

Participant Groups

Group I: Tislelizumab in conjunction with radiation therapy Experimental Treatment 1 Intervention

Participants will receive local therapy including TACE+ RT or Ablation (tumors with incomplete ablation) + RT or RT alone (for patients not eligible for TACE or Ablation) and will be screened for eligibility prior to enrollment. Once eligibility has been confirmed, Tislelizumab will be started before radiation therapy and will continue after radiation therapy. Participants who do not receive Tislelizumab for a total of two cycles will be replaced and interpreted for only toxicity analysis.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

BioGene Pharmaceutical Ltd.

Industry Sponsor

Trials

2

Recruited

40+

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

Findings from Research

Tislelizumab is a modified PD-1 antibody that effectively inhibits tumor growth in various cancers, including Hodgkin's lymphoma and lung cancer, and has received multiple approvals in China for its use.

It has a favorable safety profile with common side effects like fatigue and anemia, and it offers economic advantages over other PD-1 inhibitors, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. Zhang, L., Geng, Z., Hao, B., et al.[2023]

Tislelizumab, a PD-1 inhibitor, significantly improved the overall response rate (ORR) and disease control rate (DCR) in patients with malignant solid tumors, with odds ratios of 2.59 and 1.78, respectively, based on a meta-analysis of seven phase III trials involving 3478 participants.

The treatment also demonstrated improved overall survival (OS) and progression-free survival (PFS), with hazard ratios of 0.71 and 0.68, indicating that tislelizumab is an effective option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. Abushanab, AK., Mustafa, MT., Mousa, MT., et al.[2023]

In a phase 2 study involving 249 patients with previously treated advanced hepatocellular carcinoma (HCC), tislelizumab showed an objective response rate of 13%, indicating its potential effectiveness as a treatment option.

The treatment was generally well-tolerated, with only 15% of patients experiencing grade ≥3 treatment-related adverse events, and no deaths attributed to the treatment, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial. Ren, Z., Ducreux, M., Abou-Alfa, GK., et al.[2023]

In a phase 3 clinical trial with 674 patients, tislelizumab showed noninferior overall survival compared to sorafenib for first-line treatment of unresectable hepatocellular carcinoma (HCC), with median survival times of 15.9 months versus 14.1 months, respectively.

Tislelizumab had a higher objective response rate (14.3% vs 5.4%) and a more durable response duration (36.1 months vs 11.0 months) compared to sorafenib, while also demonstrating a better safety profile with fewer severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. Qin, S., Kudo, M., Meyer, T., et al.[2023]

Tislelizumab, a monoclonal antibody targeting PD-1, shows promising preliminary antitumor activity in patients with advanced unresectable hepatocellular carcinoma (HCC), which typically has a poor prognosis with a median life expectancy of about 1 year.

This study is a Phase III trial that directly compares the efficacy, safety, and tolerability of tislelizumab against sorafenib, a standard treatment for unresectable HCC, aiming to establish tislelizumab as a viable first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RATIONALE 301 study: tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. Qin, S., Finn, RS., Kudo, M., et al.[2019]

Tislelizumab, an anti-PD-1 monoclonal antibody, shows improved progression-free survival and objective response rates in treating non-small cell lung cancer (NSCLC), especially when combined with chemotherapy, based on a review of four randomized controlled trials involving 1565 patients.

While tislelizumab is generally effective, it is associated with treatment-emergent adverse events, including significant hematologic issues and immune-mediated effects like hypothyroidism and pneumonitis, with a mortality rate from these events ranging from 3.2% to 4.2%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. Daei Sorkhabi, A., ZareDini, M., Fazlollahi, A., et al.[2023]

In a phase II study with 70 patients suffering from relapsed/refractory classical Hodgkin lymphoma, tislelizumab showed a high overall response rate of 87.1% and a complete response rate of 67.1% after a median follow-up of 33.8 months, indicating its efficacy as a treatment option.

The treatment demonstrated a favorable safety profile, with 97.1% of patients experiencing treatment-related adverse events, but only 31.4% having severe (grade ≥3) events, and just 8.6% discontinuing treatment due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. Song, Y., Gao, Q., Zhang, H., et al.[2023]

References

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

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. [2023]

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

Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial. [2023]

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

Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. [2023]

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

RATIONALE 301 study: tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. [2019]

6. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. [2023]

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

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. [2023]