Tislelizumab + Chemotherapy for Lung Cancer

Recruiting at 91 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

400 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the antitumor activity, safety, and tolerability of tislelizumab plus investigational agent(s) with or without chemotherapy. This study is structured as a master protocol with separate sub- studies. Sub-study 1 includes participants with non-small cell lung cancer (NSCLC) with high programmed cell death protein ligand-1 (PD-L1) expression (≥ 50%), and Sub-study 2 includes participants with NSCLC with low or negative (PD-L1) expression (\< 50%).

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.

What data supports the idea that Tislelizumab + Chemotherapy for Lung Cancer is an effective treatment?

The available research shows that Tislelizumab, when combined with chemotherapy, may improve outcomes for patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy alone. Specifically, the RATIONALE 304 trial suggests that this combination could lead to better results for patients with advanced nonsquamous NSCLC. This indicates that adding Tislelizumab to chemotherapy might be more effective than using chemotherapy by itself. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Tislelizumab + Chemotherapy for Lung Cancer?

Research shows that Tislelizumab, when combined with chemotherapy, may improve outcomes for patients with advanced non-small cell lung cancer compared to chemotherapy alone. Tislelizumab is designed to enhance the immune system's ability to fight cancer by targeting a specific protein (PD-1) that helps cancer cells evade immune detection. ^{1 2 3 4 5}

What safety data is available for Tislelizumab plus chemotherapy in lung cancer treatment?

Tislelizumab, an anti-PD-1 monoclonal antibody, has been evaluated for safety in various studies. It has an acceptable safety profile with common adverse effects including fatigue, anemia, and decreased neutrophil count. Serious adverse events have included respiratory infection or failure, and hepatic injury. In a study on urothelial carcinoma, the most common treatment-related adverse events were anemia (27%) and pyrexia (19%), with anemia (7%) and hyponatremia (5%) being the only grade 3-4 events occurring in ≥ 5% of patients. Three deaths were possibly related to the treatment. Overall, Tislelizumab has shown a manageable safety profile in clinical trials. ^{1 3 6 7 8}

Is the combination of Tislelizumab and chemotherapy safe for treating lung cancer?

Tislelizumab, when used alone or with chemotherapy, has shown an acceptable safety profile in treating various cancers, including lung cancer. Common side effects include fatigue, anemia (low red blood cell count), and decreased neutrophil count (a type of white blood cell), while serious risks involve respiratory infections or liver damage. Overall, it is considered manageable in terms of safety. ^{1 3 6 7 8}

Is the drug Tislelizumab a promising treatment for lung cancer?

Yes, Tislelizumab is a promising drug for lung cancer. It is designed to work with the body's immune system to fight cancer cells more effectively. Studies show that when combined with chemotherapy, it can improve outcomes for patients with advanced lung cancer. ^{1 3 4 5 9}

What makes the drug Tislelizumab unique for lung cancer treatment?

Tislelizumab is unique because it is an anti-PD-1 monoclonal antibody specifically engineered to reduce binding to certain receptors on immune cells, which helps prevent the immune system from clearing T-cells that fight cancer. This design aims to improve its effectiveness in treating non-small cell lung cancer when combined with chemotherapy. ^{1 3 4 5 9}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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, 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]

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]

References

1. 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]

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

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]

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

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

5. United States 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. [2021]

6. England 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. [2023]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. [2023]