Ociperlimab + Tislelizumab vs Pembrolizumab for Lung Cancer

Not currently recruiting at 476 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment combination for a specific type of lung cancer. It compares the effects of two drugs, ociperlimab and tislelizumab, with a known treatment, pembrolizumab (an immunotherapy drug). The focus is on patients with non-small cell lung cancer (NSCLC) that has either spread or cannot be treated with surgery or radiation. Suitable candidates have lung cancer with a high level of PD-L1 (a protein) and have not yet received treatment for their metastatic cancer. The goal is to determine if the new combination is safer and more effective than the existing option. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

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.

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

Research has shown that the combination of tislelizumab and ociperlimab is generally well-tolerated. In one study, 60% of patients experienced serious side effects, but these were manageable. This indicates that while some patients had strong reactions, doctors could treat or control them.

For pembrolizumab, which is already approved for other uses, long-term studies have demonstrated its safety for patients with lung cancer. Over five years, it has remained effective and safe, providing a strong track record for its use.

Overall, both treatment options have shown safety, though some patients may experience side effects. It is important to discuss potential risks and benefits with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they offer potentially novel ways to fight the disease. Ociperlimab, when combined with Tislelizumab, could provide a unique one-two punch against cancer cells by enhancing the immune system's ability to recognize and destroy them. Unlike standard treatments like Pembrolizumab, which targets a single protein, this combination uses Tislelizumab to block the PD-1 pathway and Ociperlimab to target TIM-3, potentially overcoming resistance seen with other therapies. This dual-action approach may lead to improved outcomes for patients who have limited options with current treatments.

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

This trial will compare the combination of ociperlimab and tislelizumab with pembrolizumab for treating non-small cell lung cancer (NSCLC). Research has shown that using ociperlimab and tislelizumab together, which participants in this trial may receive, can help treat NSCLC by shrinking tumors and extending the time patients live without their cancer worsening. Studies suggest it might be more effective than some other treatments for advanced NSCLC.

Pembrolizumab, another treatment option in this trial, has a proven track record. It significantly increases survival rates for patients with advanced NSCLC, with up to 22% of patients living five years or more. It is widely used and considered a standard treatment for this type of cancer. Both treatment options are supported by evidence, but they may work differently for each person. ^{1 5 6 7 8}

Who Is on the 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

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/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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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 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]

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]

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]

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]

Citations

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Five-Year Outcomes With Pembrolizumab Versus ... With 5-year OS rates of up to 22%, these data support the continued use of pembrolizumab monotherapy as a standard-of-care treatment for previously untreated PD ...

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Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00123-1/fulltext

Subcutaneous versus intravenous pembrolizumab, in ... The OS event rate was comparable between the pembrolizumab s.c. and pembrolizumab i.v. arms (24.3% versus 29.4%). As of data cut-off, the median ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02142738

NCT02142738 | Study of Pembrolizumab (MK-3475) ... This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies.

5. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%). In KEYNOTE⁠-⁠671, adverse reactions ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39952082/

Five-year efficacy and safety of pembrolizumab as first-line ... The real-world 5-year survival rate of NSCLC cases with PD-L1 ≥ 50 % treated with first-line pembrolizumab was comparable to that in a clinical trial.

7. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(24)00081-0/fulltext

5-Year Real-World Outcomes With Frontline ... With 5-year follow-up in a real-world population, frontline pembrolizumab monotherapy continues to demonstrate long-term effectiveness.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02885

Five-Year Outcomes With Pembrolizumab Versus ... The estimated 5-year OS rates were 11.9% and 7.4% in the pembrolizumab and chemotherapy groups, respectively (Data Supplement). Safety. In the ...