What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC), such as PD-1 inhibitors like Pembrolizumab, can cause immune-related adverse events (irAEs) including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. When combined with chemotherapy, additional side effects may include nausea, vomiting, fatigue, hair loss, and increased risk of infection. Severe treatment-related adverse effects (≥grade 3) are also observed, such as severe pneumonitis and other organ-specific toxicities.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been FDA approved for the treatment of NSCLC, particularly for patients with high PD-L1 expression (≥50%). Other similar immune checkpoint inhibitors include Nivolumab (PD-1 inhibitor) and Atezolizumab (PD-L1 inhibitor), both of which have been approved for use in various settings of NSCLC. These drugs have shown efficacy in improving overall survival and progression-free survival in patients with advanced NSCLC, either as monotherapy or in combination with chemotherapy.

What other types of research exist?

Promising novel alternatives to Pembrolizumab/Vibostolimab for NSCLC patients include: 1) Tislelizumab combined with chemotherapy, which has shown improved median PFS and ORRs in squamous cell NSCLC. 2) Sintilimab combined with chemotherapy, which has demonstrated improved PFS in both squamous and nonsquamous carcinoma and is under FDA review. 3) Durvalumab plus Tremelimumab, particularly for patients with high tumor mutational burden (TMB), which has shown improved OS in post-hoc analyses.

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Alkylating agents

Pembrolizumab/Vibostolimab + Chemoradiotherapy for Non-Small Cell Lung Cancer

Phase 3

Recruiting

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has no evidence of metastatic disease, indicating Stage IV NSCLC, in whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET) or FDG-PET/computed tomography (CT) and CT or magnetic resonance imaging (MRI) scans of diagnostic quality of chest, abdomen, pelvis and brain

Is determined to have unresectable, Stage III NSCLC as documented by a multidisciplinary tumor board or by the treating physician in consultation with a thoracic surgeon

Must not have

Has received colony-stimulating factors (e.g., Granulocyte Colony-Stimulating Factor [G-CSF], Granulocyte Macrophage Colony-Stimulating Factor [GM-CSF], or recombinant erythropoietin) within 28 days prior to the first dose of study intervention

Has had an allogenic tissue/solid organ transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 75 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests a combination of two drugs, pembrolizumab and vibostolimab, along with standard chemotherapy and radiation in patients with advanced lung cancer that cannot be surgically removed. The goal is to see if this combination can better control the disease and improve survival compared to another drug, durvalumab. These drugs help the immune system attack cancer cells more effectively.

Who is the study for?

This trial is for adults with Stage III Non-small Cell Lung Cancer (NSCLC) who haven't had previous treatments. They must have a life expectancy of at least 6 months, be able to provide a tumor tissue sample, and not show signs of cancer spread in scans. Participants should be physically capable (ECOG status 0 or 1) and cannot have an active infection, recent vaccines, other cancer treatments within the last month, autoimmune diseases treated in the past two years, or certain medical conditions.

What is being tested?

The study tests pembrolizumab/vibostolimab with chemoradiotherapy (cCRT), followed by more pembrolizumab/vibostolimab against cCRT followed by durvalumab. It aims to see if the first combination is better for extending survival without cancer progression and overall survival in patients whose tumors express PD-L1 protein.

What are the potential side effects?

Possible side effects include immune-related reactions like inflammation in various organs due to pembrolizumab/vibostolimab or durvalumab; chemotherapy may cause nausea, fatigue, hair loss; radiotherapy might lead to skin irritation and fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My scans show no signs of cancer spread beyond my lungs.

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My lung cancer is at Stage III and cannot be removed by surgery.

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My cancer can be measured and has a targetable lesion.

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My lung cancer diagnosis is confirmed by lab tests.

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My lung cancer is at stage IIIA, IIIB, or IIIC.

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I haven't had any treatment for my Stage III lung cancer.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have received drugs to boost my white blood cells within the last 28 days.

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I have received an organ or tissue transplant from another person.

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I cannot stop taking aspirin or NSAIDs for a few days around my treatment.

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I am currently being treated for an infection.

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I have been treated for an autoimmune disease in the last 2 years.

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I have had radiation therapy to my chest area before.

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I have another cancer that has gotten worse or needed treatment in the last 5 years.

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I cannot or will not take folic acid, vitamin B12, and dexamethasone.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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I have a history of Hepatitis B or an active Hepatitis C infection.

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I have or had lung inflammation that needed steroids.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 75 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 75 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 75 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival (OS) For All Participants

Overall Survival (OS) For Participants With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%

Progression-Free Survival (PFS) For All Participants

+1 more

Secondary study objectives

Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 For All Participants

Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 For Participants With PD-L1 TPS ≥1%

Change from Baseline in Cough Score (Item 31) on the EORTC QLQ-LC13 For Participants With PD-L1 TPS ≥1%

+23 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: pembrolizumab/vibostolimab coformulation+chemotherapy+radiotherapyExperimental Treatment7 Interventions

For the first 3 cycles, participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) intravenously (IV) on Day 1 plus 3 cycles of investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy (60 Gray \[Gy\] in 2 Gy fractions for 30 days total) during Cycles 2, 3. Participants receive pembrolizumab/vibostolimab for Cycles 4-20 or until discontinuation (up to \~14 months). Cycles 1-20 are 21-day cycles. Investigator's choice of chemotherapy: cisplatin 75 mg/m\^2 and pemetrexed 500 mg/m\^2 on Day 1 of Cycles 1-3 for non-squamous histology only; cisplatin 50 mg/m\^2 on Days 1, 8 of Cycles 1-2 and Days 8, 15 of Cycle 3 and etoposide 50 mg/m\^2 on Days 1-5 of Cycles 1-2 and Days 8-12 of Cycle 3; carboplatin area under the curve (AUC) 6 mg/ml/min on Day 1 of Cycle 1 and AUC 2 mg/ml/min on Days 1, 8, 15 of Cycles 2-3 and paclitaxel 200 mg/m\^2 on Day 1 of Cycle 1 and 45 mg/m\^2 on Days 1, 8, 15 of Cycles 2-3.

Group II: chemotherapy+radiotherapy+durvalumabActive Control7 Interventions

For the first 3 cycles, participants will receive investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy (60 Gy in 2 Gy fractions for 30 days total) during Cycles 2 and 3. Following concurrent chemoradiotherapy (cCRT), participants receive durvalumab 10 mg/kg every 2 weeks for up to an additional 26 cycles or until discontinuation (up to approximately 14 months). cCRT Cycles 1-3=21-day cycles; durvalumab Cycles 1-26=14-day cycles. Investigator's choice of chemotherapy: cisplatin 75 mg/m\^2 and pemetrexed 500 mg/m\^2 on Day 1 of Cycles 1-3 for non-squamous histology only; cisplatin 50 mg/m\^2 on Days 1, 8 of Cycles 1-2 and Days 8, 15 of Cycle 3 and etoposide 50 mg/m\^2 on Days 1-5 of Cycles 1-2 and Days 8-12 of Cycle 3; carboplatin area under the curve (AUC) 6 mg/ml/min on Day 1 of Cycle 1 and AUC 2 mg/ml/min on Days 1, 8, 15 of Cycles 2-3 and paclitaxel 200 mg/m\^2 on Day 1 of Cycle 1 and 45 mg/m\^2 on Days 1, 8, 15 of Cycles 2-3.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

etoposide

1994

Completed Phase 3

~9300

carboplatin

2010

Completed Phase 3

~4790

cisplatin

1997

Completed Phase 3

~3290

pemetrexed

2005

Completed Phase 3

~5000

paclitaxel

1996

Completed Phase 3

~4310

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) often involve immune checkpoint inhibitors, which help the immune system recognize and attack cancer cells. Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 protein on T cells from binding to PD-L1 on cancer cells, thereby preventing the 'off' signal that stops T cells from attacking the cancer. Vibostolimab, a TIGIT inhibitor, works by blocking the TIGIT protein, which also helps to enhance T cell activity against cancer cells. These mechanisms are crucial for NSCLC patients as they can lead to more effective immune responses against tumors, potentially improving survival rates and outcomes.