BGB-A425 + LBL-007 + Tislelizumab for Solid Cancers

Recruiting at 93 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BeiGene

Must not be taking: Antibacterials, Antifungals, Antivirals, others

Disqualifiers: Autoimmune diseases, Brain metastasis, Diabetes, Cardiac issues, others

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

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

Compensation: Varies

Number of Visits: Unknown

114 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing new drug combinations to help the immune system fight advanced solid tumors better. It targets patients who do not respond well to existing treatments by blocking proteins that cancer cells use to hide from the immune system.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had chemotherapy, radiotherapy, immunotherapy, or any investigational therapies within 28 days (or 14 days for Phase 2 Dose Expansion) before starting the study drugs. Please consult with the trial team for more details.

What data supports the idea that BGB-A425 + LBL-007 + Tislelizumab for Solid Cancers is an effective drug?

The available research shows that Tislelizumab, a part of the drug combination, has demonstrated promising anti-tumor effects in various solid cancers, including lung, liver, and gastric cancers. It has been approved in China for several cancer types due to its effectiveness. Tislelizumab is noted for its ability to help the immune system fight cancer cells by blocking a pathway that tumors use to hide from immune attacks. Additionally, it has an economic advantage over other similar drugs, making it a potentially more accessible option for patients. While specific data on the combination with BGB-A425 and LBL-007 is not detailed, the individual success of Tislelizumab in treating solid tumors supports the potential effectiveness of the combination. ^{1 2 3 4 5}

What safety data is available for the treatment BGB-A425 + LBL-007 + Tislelizumab for solid cancers?

The safety data for Tislelizumab, a component of the treatment, indicates that it has an acceptable safety profile. Common adverse effects include fatigue, anemia, and decreased neutrophil count, while more serious events have involved respiratory infection or failure, and hepatic injury. Tislelizumab has been studied in various solid tumors and is approved in China for several cancer types. However, specific safety data for the combination of BGB-A425, LBL-007, and Tislelizumab is not detailed in the provided research. ^{1 3 4 5 6}

Is the drug Tislelizumab a promising treatment for solid cancers?

Yes, Tislelizumab is a promising drug for treating solid cancers. It has shown effective anti-tumor effects in various cancers like lung, liver, and gastric cancer. It is approved in China for several cancer types and has potential for more approvals. It also has an economic advantage over similar drugs, making it a valuable option for cancer treatment. ^{1 2 5 7 8}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with certain advanced solid tumors, including specific types of head and neck, lung, or renal cancers. Participants must have a good performance status (able to carry out daily activities), proper organ function, and no major health issues like severe allergies to monoclonal antibodies or uncontrolled diabetes. They should not have received other recent cancer treatments or be part of another clinical study.

Inclusion Criteria

Phase 2 Dose-Expansion: Participants with one of the following histologically or cytologically confirmed solid tumors: For HNSCC participants in cohort 1,4 and 6 (PD-L1 positive): Recurrent/metastatic head and neck squamous cell cancer of the oral cavity, oropharynx, hypopharynx, and/or larynx whose tumor is not amenable to local therapy with curative intent (ie, surgery or radiation therapy with or without chemotherapy • For NSCLC participants in Cohort 2, 5 and 7 (PD-L1 positive): Locally recurrent Stage IIIB, stage IIIC or Stage IV squamous or non-squamous non-small cell lung cancer • For RCC participants in Cohort 3: Locally advanced unresectable or metastatic and histologically confirmed renal cell carcinoma with a clear cell histology

I have an advanced cancer that cannot be removed by surgery and have tried or cannot undergo standard treatment.

I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

You are currently enrolled in another clinical trial for a different treatment.

There may be other rules that apply to who can or cannot participate in the study.

I am not on any strong antibiotics, antifungals, or antivirals.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Dose escalation of BGB-A425 in combination with Tislelizumab in participants with advanced solid tumors to determine the recommended phase 2 dose (RP2D)

Approximately 2 years

Phase 2 Safety Lead-in

Dose escalation for Cohort A (LBL-007 + Tislelizumab) and Cohort B (BGB-A425 + LBL-007 + Tislelizumab) to determine the RP2D

Approximately 2 years

Phase 2 Dose Expansion

Further explore the safety and clinical activity of BGB-A425 and LBL-007 in combination with Tislelizumab in participants with NSCLC, HNSCC, and RCC

Approximately 2-3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BGB-A425
• LBL-007
• Tislelizumab

Trial Overview The study is testing the combination of three drugs: BGB-A425, LBL-007, and Tislelizumab in patients with advanced solid tumors. It's an early-phase trial that includes both initial dose-finding (Phase 1) and later-stage evaluation (Phase 2) to assess safety and effectiveness.

Participant Groups

Group I: Phase 2 Safety Lead-in Experimental Treatment 3 Interventions

Dose escalation for Cohort A (LBL-007 + Tislelizumab) and Cohort B (BGB-A425 + LBL-007 + Tislelizumab) in participants with advanced solid tumors

Group II: Phase 2 Dose Expansion Experimental Treatment 3 Interventions

Further explore the safety and clinical activity of BGB-A425 and LBL-007 in combination with Tislelizumab in participants with NSCLC, HNSCC and RCC

Group III: Phase 1 Dose Escalation Experimental Treatment 2 Interventions

Dose escalation of BGB-A425 in combination with Tislelizumab in participants with advanced solid tumors

Tislelizumab is already approved in European Union, United States for the following indications:

Approved in European Union as Tizveni for:

• Non-small cell lung cancer (first and second line)
• Locally advanced or metastatic esophageal squamous cell carcinoma (second line)

Approved in United States as Tevimbra for:

• Unresectable or metastatic esophageal squamous cell carcinoma (second line)

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

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]

In a phase IA/IB study involving 451 patients with advanced solid tumors, tislelizumab demonstrated an acceptable safety profile, with most adverse events being mild (grade 1-2), and only 5.3% of patients discontinuing treatment due to side effects.

Tislelizumab showed promising antitumor activity, with 18% of patients in phase IA and 12% in phase IB achieving confirmed objective responses, leading to the recommendation of a dosing schedule of 200 mg every 3 weeks for future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. Desai, J., Deva, S., Lee, JS., et al.[2021]

Tislelizumab, an anti-PD-1 monoclonal antibody, shows promising efficacy and a manageable safety profile in treating advanced non-small cell lung cancer (NSCLC), with higher affinity to PD-1 compared to other similar therapies like pembrolizumab and nivolumab.

The drug's unique design minimizes binding to macrophages, potentially reducing resistance to treatment, and ongoing trials are exploring its effectiveness in combination with other therapies, which could enhance its role in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC). Liu, SY., Wu, YL.[2022]

In a study involving 180 patients with advanced solid tumors, the combination of pamiparib and tislelizumab demonstrated an overall objective response rate (ORR) of 20%, with the highest response (47.4%) observed in patients with triple-negative breast cancer (TNBC) who had BRCA1/2 mutations or homologous recombination deficiency.

While the treatment showed promising antitumor activity, it was associated with a significant incidence of treatment-emergent adverse events, with 61.7% of patients experiencing grade 3 or higher side effects, indicating that while the therapy is effective, careful monitoring for safety is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. Friedlander, M., Mileshkin, L., Lombard, J., 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]

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]

Tislelizumab is an anti-PD-1 monoclonal antibody developed as an immunotherapy for cancer, specifically approved in December 2019 in China for relapsed or refractory classical Hodgkin's lymphoma after at least two prior chemotherapy treatments.

The drug has shown promise in treating both hematological cancers and advanced solid tumors, indicating its potential for future approvals in additional cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: First Approval. Lee, A., Keam, SJ.[2020]

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

Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC). [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. [2023]

5. 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]

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]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Tislelizumab: First Approval. [2020]