Pembrolizumab/Vibostolimab + Chemoradiotherapy for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+168 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Merck Sharp & Dohme Corp.
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain medications like chronic systemic steroids, immunosuppressive therapy, or NSAIDs around the time of pemetrexed administration. It's best to discuss your current medications with the trial team.
What data supports the idea that Pembrolizumab/Vibostolimab + Chemoradiotherapy for Non-Small Cell Lung Cancer is an effective treatment?
The available research shows that adding pembrolizumab to chemotherapy significantly improves survival and response rates in patients with non-small cell lung cancer. For example, in the KEYNOTE-407 study, patients who received pembrolizumab with chemotherapy lived longer and had better outcomes compared to those who received chemotherapy alone. Additionally, the combination of vibostolimab and pembrolizumab has shown promise in treating solid tumors, indicating its potential effectiveness. These findings suggest that Pembrolizumab/Vibostolimab + Chemoradiotherapy could be an effective treatment option for non-small cell lung cancer.
12345What safety data is available for the treatment of Pembrolizumab/Vibostolimab with Chemoradiotherapy in NSCLC?
The combination of Pembrolizumab and Vibostolimab is generally well tolerated and shows antitumor activity. Pembrolizumab, when combined with chemotherapy, has been shown to improve survival rates in NSCLC with minimal severe toxicity. However, immune checkpoint inhibitors like Pembrolizumab can cause adverse effects such as pneumonitis in 1%-5% of patients. Combining Pembrolizumab with radiotherapy has shown slight toxicity but good benefits. Overall, the treatment is considered effective with manageable safety concerns.
23567Is the drug combination of Pembrolizumab/Vibostolimab with Chemoradiotherapy promising for treating Non-Small Cell Lung Cancer?
Yes, the combination of Pembrolizumab/Vibostolimab with Chemoradiotherapy is promising for treating Non-Small Cell Lung Cancer. Research shows that this drug combination is well tolerated, has antitumor activity, and can improve survival outcomes and provide long-lasting responses.
278910Eligibility Criteria
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.Inclusion Criteria
My scans show no signs of cancer spread beyond my lungs.
My lung cancer is at Stage III and cannot be removed by surgery.
My cancer can be measured and has a targetable lesion.
My lung cancer diagnosis is confirmed by lab tests.
My lung cancer is at stage IIIA, IIIB, or IIIC.
I haven't had any treatment for my Stage III lung cancer.
Exclusion Criteria
I have received drugs to boost my white blood cells within the last 28 days.
I have received an organ or tissue transplant from another person.
I cannot stop taking aspirin or NSAIDs for a few days around my treatment.
I am currently being treated for an infection.
I have been treated for an autoimmune disease in the last 2 years.
I have had radiation therapy to my chest area before.
I have another cancer that has gotten worse or needed treatment in the last 5 years.
I cannot or will not take folic acid, vitamin B12, and dexamethasone.
I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.
I have a history of Hepatitis B or an active Hepatitis C infection.
I have or had lung inflammation that needed steroids.
Participant Groups
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.
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.
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Moffitt Cancer Center ( Site 2818)Tampa, FL
University of Missouri Hospital ( Site 2839)Columbia, MO
VA West Los Angeles Medical Center ( Site 2808)Los Angeles, CA
VA Long Beach Healthcare System ( Site 2831)Long Beach, CA
More Trial Locations
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Who is running the clinical trial?
Merck Sharp & Dohme Corp.Lead Sponsor
Merck Sharp & Dohme LLCLead Sponsor
References
A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. [2021]In the randomized KEYNOTE-407 study (ClinicalTrials.gov, NCT02775435), pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC. We report updated efficacy outcomes from the protocol-specified final analysis and, for the first time, progression on next line of treatment.
An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]Combination of vibostolimab and pembrolizumab is well tolerated and has antitumor activity.
Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study.
Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. [2020]In the phase 3 KEYNOTE-407 study, the addition of pembrolizumab to carboplatin-paclitaxel/nab-paclitaxel significantly improved overall survival, progression-free survival, and objective response rate in patients with previously untreated metastatic squamous non-small-cell lung cancer (NSCLC), with little impact on severe toxicity. We present patient-reported outcomes (PROs) from KEYNOTE-407.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report. [2018]Pembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and good benefits in recent clinical trials. However, patients infected with human immunodeficiency virus were excluded from most trials because it was assumed that their anti-tumor immunity was compromised compared with immunocompetent patients.
Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]Pembrolizumab is a highly selective IgG4 kappa isotype monoclonal antibody against the programmed cell death-1 (PD-1) molecule. In the treatment of non-small cell lung cancer (NSCLC), pembrolizumab has demonstrated significant efficacy, significant survival outcomes, long-lasting responses, and a good safety profile compared with cytotoxic chemotherapy.
Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. [2022]Administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non-small cell lung cancer (NSCLC).
Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response.