Tislelizumab + Chemotherapy for Lung Cancer

Not currently recruiting at 103 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BeiGene

Must not be taking: Chinese herbal medicines

Disqualifiers: Small cell lung cancer, actionable mutations, 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: Unknown

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a drug called tislelizumab (Tevimbra) when combined with other treatments for non-small cell lung cancer (NSCLC). Researchers aim to determine if adding drugs like BGB-A445 (an experimental treatment) or LBL-007 (an Anti-LAG-3 monoclonal antibody), with or without chemotherapy, enhances cancer treatment. The study includes two main groups: one for individuals with high PD-L1 levels (a protein linked to cancer growth) and another for those with low or no PD-L1. Suitable participants have advanced or recurrent NSCLC, have not received certain treatments before, and know their PD-L1 status. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received Chinese herbal medicine or Chinese patent medicines used to control cancer within 14 days before joining the trial.

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, you cannot have received any Chinese herbal medicine or Chinese patent medicines used to control cancer within 14 days before joining the trial.

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

Research shows that tislelizumab, a type of immune therapy, is generally safe when used alone or with chemotherapy. It has been used to treat various cancers and is usually well-tolerated. Some studies suggest it might be safer than traditional chemotherapy.

When combined with BGB-A445, no new safety concerns have emerged. BGB-A445, whether used alone or with tislelizumab, has been well-tolerated by people with advanced cancers.

Tislelizumab combined with LBL-007 is currently under study. Previous research in similar contexts indicates this combination is reasonably safe.

For the combination of tislelizumab with BGB-15025, early studies found it to be generally tolerable, with no serious side effects affecting the dose for participants.

These findings suggest a good safety record so far, but joining a trial requires understanding potential risks. Always consult a doctor first. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore new combinations involving Tislelizumab, potentially enhancing its effectiveness against lung cancer. Unlike traditional treatments like chemotherapy and other immune checkpoint inhibitors, these new combinations bring in BGB-A445, LBL-007, and BGB-15025, which are designed to work synergistically with Tislelizumab. Tislelizumab is an immune checkpoint inhibitor that targets PD-1, but the addition of these agents aims to further boost the immune system's attack on cancer cells. These combinations could offer improved outcomes by potentially increasing the precision and strength of the immune response in lung cancer patients.

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

Research has shown that tislelizumab effectively treats lung cancer, with studies indicating a high rate of tumor shrinkage and disease control. Specifically, tislelizumab achieved a 54% rate of tumor shrinkage and an 86% rate of disease control in patients with advanced lung cancer. In this trial, participants may receive different treatment combinations. One arm will study the combination of tislelizumab with BGB-A445, which has demonstrated strong immune-boosting effects and is generally well tolerated. Another arm will evaluate LBL-007 with tislelizumab, which has shown promise as a first treatment option for advanced cancer. Additionally, preliminary results for BGB-15025 with tislelizumab suggest it is well tolerated and may help fight tumors. These findings support the potential effectiveness of these treatment combinations in lung cancer. ^{6 7 8 9 10}

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 advanced or recurrent non-small cell lung cancer (NSCLC) that can't be treated with surgery. They should not have had prior treatments for metastatic NSCLC, must have a performance status showing they're mostly active and able to care for themselves, and at least one measurable tumor lesion. Patients are divided based on their tumor's PD-L1 protein levels.

Inclusion Criteria

At least 1 measurable lesion as defined per RECIST v1.1

My tumor has been tested for PD-L1 and shows expression.

My lung cancer is advanced, cannot be cured by surgery or chemoradiotherapy, and may have spread.

Exclusion Criteria

My cancer has a mutation that can be treated with specific drugs.

I haven't taken any Chinese herbal or patent medicines for cancer in the last 14 days.

I've had treatments targeting immune checkpoints but have been treatment-free for 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tislelizumab in combination with investigational agents with or without chemotherapy

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• BGB-A445
• Carboplatin
• Cisplatin
• LBL-007
• Nab paclitaxel
• Paclitaxel
• Pemetrexed
• Tislelizumab

Trial Overview The study tests the effectiveness of Tislelizumab combined with other investigational drugs and possibly chemotherapy in treating NSCLC. It has two parts: one part includes patients whose tumors express high levels of PD-L1 protein, while the other involves those with low or no expression of this protein.

How Is the Trial Designed?

Group I: Sub-study 2: Arm 3B Experimental Treatment 7 Interventions

Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025

Group II: Sub-study 2: Arm 2B Experimental Treatment 7 Interventions

Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007

Group III: Sub-study 2: Arm 1B Experimental Treatment 7 Interventions

Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445

Group IV: Sub-study 1: Arm 3A Experimental Treatment 2 Interventions

Tislelizumab + BGB-15025

Group V: Sub-study 1: Arm 2A Experimental Treatment 2 Interventions

Tislelizumab + LBL-007

Group VI: Sub-study 1: Arm 1A Experimental Treatment 2 Interventions

Tislelizumab + BGB-A445

Group VII: Sub-study 1: Reference Arm Tislelizumab alone Active Control 1 Intervention

Tislelizumab alone

Group VIII: Sub-study 2: Reference Arm Active Control 6 Interventions

Tislelizumab + investigator's choice of histology-appropriate chemotherapy

BGB-A445 is already approved in European Union, United States, China for the following indications:

Approved in European Union as Tevimbra for:

• Unresectable, locally advanced or metastatic esophageal squamous cell carcinoma after prior platinum-based chemotherapy
• HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma in combination with platinum- and fluoropyrimidine-based chemotherapy
• Non-small cell lung cancer

Approved in United States as Tevimbra for:

• Unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor

Approved in China as Tevimbra for:

• Esophageal squamous cell carcinoma

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

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 of 40 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), preoperative treatment with tislelizumab plus chemotherapy resulted in a high objective response rate of 65%, with a major pathological remission (MPR) rate of 56.52% and a pathological complete remission (pCR) rate of 34.78%.

The treatment was associated with acceptable safety, as only 4 patients experienced grade 3-4 treatment-related adverse events, and there were no perioperative deaths, while the 1-year progression-free survival rate was 85% and the overall survival rate was 90%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of tislelizumab plus chemotherapy as preoperative treatment in potentially resectable locally advanced non-small cell lung cancer patients. Huang, X., Zhu, L., Liu, J., 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]

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 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]

In a phase 3 trial involving 332 patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC), the combination of tislelizumab and chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone, with a median PFS of 9.7 months versus 7.6 months.

The addition of tislelizumab also resulted in higher response rates and longer duration of response, making it a promising first-line treatment option for patients with advanced nsq-NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. Lu, S., Wang, J., Yu, Y., et al.[2021]

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]

In a study of 115 patients with recurrent or metastatic cervical cancer treated with tislelizumab, the overall response rate was 39.1%, and the median progression-free survival was 19.6 months, indicating promising antitumor activity.

Baseline serum C-reactive protein (CRP) levels and the CRP-to-albumin ratio (CAR) were identified as independent risk factors for predicting the efficacy and prognosis of tislelizumab treatment, with higher levels associated with shorter progression-free and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. Zheng, X., Gu, H., Cao, X., et al.[2023]

Tislelizumab, an anti-PD-1 monoclonal antibody, showed a confirmed objective response rate of 24% in patients with PD-L1-positive urothelial carcinoma who had progressed after platinum therapy, indicating its efficacy in this challenging patient population.

The treatment had a manageable safety profile, with the most common adverse events being anemia (27%) and pyrexia (19%), and only a small percentage of patients experiencing severe side effects, suggesting that tislelizumab is a viable option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. Ye, D., Liu, J., Zhou, A., et al.[2022]

Citations

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NCT05635708 | A Study of Tislelizumab in Combination ... The purpose of this study is to assess the antitumor activity, safety, and tolerability of tislelizumab plus investigational agent(s) with or without ...

2. beonemedinfo.com beonemedinfo.com/CongressDocuments/Deva_BGB-A317-15025-101_ASCO_Poster_2024.pdf

A First-in-Human Phase 1a Dose-Escalation Study of BGB- ... received BGB-15025 + tislelizumab. • The most common tumors were kidney cancer, non-small cell lung cancer, cervical cancer, colorectal ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2585

A first-in-human phase 1a dose-escalation study of BGB ... Conclusions: These preliminary results show BGB-15025 mono tx or combo tx with TIS was generally tolerable. The antitumor activity of BGB-15025 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40230743/

Efficacy of Tislelizumab in Lung Cancer Treatment The primary outcomes assessed were overall survival (OS) and progression-free survival (PFS). Four phase-III RCTs involving 1,837 patients were ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-of-tislelizumab-lbl-007-and-bgb-15025-in-patients-with-advanced-non-small-cell-lung-cancer/

Study of Tislelizumab, LBL-007, and BGB-15025 in ... This study investigates the efficacy of Tislelizumab, in combination with LBL-007 and BGB-15025, for treating patients with advanced ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40578840/

Long-term safety analysis of pooled data for tislelizumab as ... Tislelizumab's safety profile, as monotherapy or combined with chemotherapy, remains consistent with previous reports across tumor types.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12265466/

Long-term safety analysis of pooled data for tislelizumab as ... Tislelizumab (BGB-A317), an anti-PD-1 monoclonal antibody, has demonstrated improved survival outcomes and a manageable safety profile in ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03663205

A Study Evaluating the Efficacy and Safety of Tislelizumab ... This study evaluated the efficacy and safety of tislelizumab in combination with platinum (cisplatin or carboplatin) and pemetrexed compared with platinum ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0169500225000716

and subsequent lines in locally advanced or metastatic non ... Eighty to eighty-five percent of all new lung cancer cases are non–small cell lung cancer (NSCLC), which has a global 5-year survival rate of 24 % [2], [3], [4] ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/761232Orig1s000MultidisciplineR.pdf

761232Orig1s000 - accessdata.fda.gov These results would suggest that tislelizumab has a better-tolerated safety profile than chemotherapy. ... Safety data from Study BGB-A317-001,. BGB-A317-102, BGB ...