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

No longer recruiting at 104 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests combinations of three treatments—BGB-A425 (a humanized IgG1-variant monoclonal antibody against TIM-3), LBL-007 (an anti-LAG-3 monoclonal antibody), and tislelizumab—to evaluate their effectiveness for advanced solid tumors, including lung, head and neck, and kidney cancers. The goal is to identify safe and effective doses and understand how these treatments might combat cancer. The trial is open to individuals with these cancers who have exhausted other treatments or lack other options. Those struggling with these types of cancer and finding current treatments ineffective might find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

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.

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

Studies are examining the safety and effectiveness of combining BGB-A425 and tislelizumab. Early research shows that patients with advanced solid tumors have generally tolerated these treatments well. Common side effects include fatigue, low red blood cell count (anemia), and a decrease in a type of white blood cell. More serious, but less common, side effects have included lung infections.

Another study found that the combination of LBL-007 with tislelizumab was also well-tolerated by patients. The side effects were manageable, with fatigue being the most common issue. When all three treatments—BGB-A425, LBL-007, and tislelizumab—are used together, the side effects are similar, but some serious cases, such as breathing problems, have occurred.

These findings suggest that while the treatment is generally well-tolerated, patients should be aware of potential side effects. Discussing these risks with healthcare providers is important when considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-A425, LBL-007, and Tislelizumab for solid cancers because these treatments offer a fresh approach compared to conventional therapies. Unlike standard treatments like chemotherapy, which indiscriminately attack rapidly dividing cells, these drugs harness the immune system to target cancer cells more precisely. Tislelizumab, for instance, is a PD-1 inhibitor that helps the immune system recognize and destroy cancer cells, potentially leading to fewer side effects. BGB-A425 and LBL-007 add another layer by targeting additional pathways, which could enhance the immune response and improve outcomes for patients with advanced solid tumors. This combination could offer new hope for patients with hard-to-treat cancers like non-small cell lung cancer, head and neck squamous cell carcinoma, and renal cell carcinoma.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that combining BGB-A425, LBL-007, and tislelizumab may help treat advanced solid tumors. In this trial, participants will join different treatment arms to evaluate these combinations. Early studies indicate that BGB-A425 and tislelizumab can enhance the immune system's ability to fight cancer cells. Other studies have found that LBL-007, when used with similar treatments, is safe and may help shrink tumors. This suggests these drugs could be beneficial when standard treatments fail. Although more research is needed, the initial results are promising for patients with solid tumors. ^{2 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03744468

NCT03744468 | Study of BGB-A425 and LBL-007 in ... This is an open-label, multicenter, nonrandomized Phase 1 and 2 clinical trial evaluating various combinations of BGB-A425 and/or LBL-007 with tislelizumab.

2. ctv.veeva.com ctv.veeva.com/study/study-of-bgb-a425-and-lbl-007-in-combination-with-tislelizumab-in-advanced-solid-tumors

Study of BGB-A425 and LBL-007 in Combination With ... Study of BGB-A425 and LBL-007 in Combination With Tislelizumab in Advanced Solid Tumors ... results in the treatment of many types of tumors.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05909904

NCT05909904 | A Study of Tislelizumab in Combination ... This study will test whether tislelizumab alone and combined with other investigational agents can be used to improve treatment outcomes in participants ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-of-bgb-a425-lbl-007-and-tislelizumab-for-patients-with-advanced-head-and-neck-cancer-lung-cancer-or-kidney-cancer/

Study of BGB-A425, LBL-007, and Tislelizumab for Patients ... This clinical trial tests the effectiveness and safety of BGB-A425, LBL-007, and Tislelizumab in treating advanced Head and Neck Squamous Cell Cancer, ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-00104

Study of BGB-A425 and LBL-007 in Combination With ... This is an open-label, multicenter, nonrandomized Phase 1 and 2 clinical trial evaluating various combinations of BGB-A425 and/or LBL-007 with tislelizumab.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS3146

Bgb-A425, an investigational anti-TIM-3 monoclonal ... This phase 1/2 study will assess the safety/tolerability, pharmacokinetic (PK) profile, and antitumor activity of BGB-A425 in combination with tislelizumab in ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03744468/

Clinical Trial: NCT03744468 This study tests the safety and anti-tumor effect of BGB-A425 in combination with tislelizumab in participants with advanced solid tumors.

8. clinicaltrial.be clinicaltrial.be/fr/details/66407?only_recruiting=0&only_eligible=0

Study of BGB-A425 and LBL-007 in Combination With ... Phase 2 safety lead-in will determine the RP2D for the combination of BGB-A425, Tislelizumab and/or LBL-007. Phase 2 dose expansion will continue to evaluate ...

9. beonemedinfo.com beonemedinfo.com/CongressDocuments/Desai%20BGB-900-102%20ASCO%202020%20Poster.pdf

bgb-a425, an investigational anti-tim-3 monoclonal ... In vitro evidence demonstrated that combining BGB-A425 with tislelizumab significantly increased IFN-γ production compared with. BGB-A425 or tislelizumab ...