Ociperlimab + Tislelizumab vs Pembrolizumab for Lung Cancer

Recruiting at 425 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BeiGene

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: EGFR mutations, ALK fusion, BRAF V600E, ROS1, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 58 months

662 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, ociperlimab and tislelizumab, to see how well they work together. Tislelizumab is an anti-PD-1 antibody developed by BeiGene, showing promise in various cancers and approved in China for several uses. It targets adults with a specific type of advanced lung cancer that has high levels of a protein called PD-L1. The drugs aim to boost the body's immune system to better recognize and attack cancer cells.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug pembrolizumab for lung cancer?

Research shows that pembrolizumab significantly improves survival rates in patients with advanced non-small cell lung cancer, especially those with high levels of a protein called PD-L1. It has been approved by the FDA for treating certain types of lung cancer, demonstrating better outcomes compared to traditional chemotherapy. ^{1 2 3 4 5}

What safety information is available for pembrolizumab (Keytruda) in humans?

Pembrolizumab (Keytruda) has been associated with several immune-related side effects, including pneumonitis (lung inflammation), colitis (inflammation of the colon), hepatitis (liver inflammation), and thyroid issues. These side effects occur in a small percentage of patients and can be serious. It is important to discuss potential risks with your healthcare provider. ^{1 5 6 7 8}

How is the drug combination of Ociperlimab, Tislelizumab, and Pembrolizumab unique for lung cancer treatment?

This drug combination is unique because it combines Ociperlimab, a novel agent, with Tislelizumab and Pembrolizumab, both of which are PD-1 inhibitors that help the immune system attack cancer cells. This combination aims to enhance the immune response against lung cancer more effectively than using each drug alone. ^{1 5 9 10 11}

Research Team

Mark Socinski, MD

Principal Investigator

Advent Health Orlando

Mark Socinski, MD

Principal Investigator

Advent Health Orlando

Shun Lu

Principal Investigator

Shanghai Chest Hospital

Eligibility Criteria

This trial is for adults with advanced or recurrent non-small cell lung cancer (NSCLC) that can't be treated with surgery/radiotherapy, or metastatic NSCLC. Participants must have tumors where PD-L1 is present in at least 50% of cells and at least one measurable lesion. They should be relatively fit (ECOG ≤ 1), able to provide tissue samples, and not have had previous treatments for metastatic NSCLC.

Inclusion Criteria

My tumor shows high PD-L1 expression.

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

My lung cancer cannot be cured with surgery or radiotherapy.

Exclusion Criteria

My cancer has specific genetic changes (EGFR, ALK, BRAF V600E, or ROS1).

I have previously received immunotherapy targeting specific immune checkpoints.

I have untreated brain metastasis or active disease in the lining of my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ociperlimab + tislelizumab or pembrolizumab every 3 weeks

Up to approximately 58 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days (±14) after last dose

Treatment Details

Interventions

• Ociperlimab
• Pembrolizumab
• Placebo
• Tislelizumab

Trial Overview The study compares two groups: Arm A receives Ociperlimab plus Tislelizumab, while Arm B gets Pembrolizumab with a placebo. The main focus is on how long patients live without their disease getting worse (PFS) and overall survival time (OS), following standard tumor measurement criteria.

Participant Groups

Group I: Arm A: Tislelizumab plus Ociperlimab Experimental Treatment 2 Interventions

Participants will receive tislelizumab 200 milligrams (mg) intravenously followed by ociperlimab 900 mg intravenously once every 3 weeks.

Group II: Arm B: Pembrolizumab plus Placebo Active Control 2 Interventions

Participants will receive pembrolizumab 200 mg intravenously followed by placebo intravenously once every 3 weeks.

Group III: Arm C: Tislelizumab plus Placebo Placebo Group 2 Interventions

Participants will receive tislelizumab 200 mg intravenously followed by placebo intravenously once every 3 weeks.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

An elderly male patient on pembrolizumab developed four autoimmune toxicities, including type 1 diabetes and pneumonitis, highlighting the risk of multiple immune-related adverse events associated with this treatment.

The case suggests that aging may increase susceptibility to these adverse effects, necessitating close monitoring and prompt management, including stopping the immunotherapy and using steroids for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. Kethireddy, N., Thomas, S., Bindal, P., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

An indirect comparison of tislelizumab and pembrolizumab in combination with chemotherapy for advanced NSCLC, involving over 2,000 participants from 6 randomized trials, showed no significant differences in overall survival, progression-free survival, or objective response rates between the two treatments.

Both treatments were associated with a similar risk of severe adverse events, indicating that either tislelizumab or pembrolizumab can be considered effective and safe options for first-line therapy in advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. Guo, Y., Jia, J., Hao, Z., et al.[2023]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Real-World Data on Pembrolizumab for Pretreated Non-Small-Cell Lung Cancer: Clinical Outcome and Relevance of the Lung Immune Prognostic Index. [2022]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. [2021]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

First report of a very rare complication in a case of nonsmall cell lung carcinoma. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. [2023]

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]