Pembrolizumab + Chemotherapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Merck Sharp & Dohme LLC
Must not be taking: Antiarrhythmics, Topoisomerase inhibitors
Disqualifiers: Small cell lung cancer, Severe pulmonary compromise, Active CNS metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
Researchers are investigating new treatments for untreated advanced non-small cell lung cancer (NSCLC), which is the most common form of lung cancer and lung cancer that has spread beyond surgical removal. Standard treatments include immunotherapy, such as pembrolizumab, and chemotherapy. This study aims to determine the effectiveness of adding other treatments, including the human epidermal growth factor receptor 3-directed antibody-drug conjugate (HER3-DXd) patritumab deruxtecan, to pembrolizumab, with or without chemotherapy. The primary goals are to assess safety and efficacy of the treatments.
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, but it mentions an 'inadequate washout period' from prior therapy as an exclusion criterion, suggesting that some medications might need to be stopped before participating. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination of Pembrolizumab, Carboplatin, Paclitaxel, and Pemetrexed for lung cancer?
Research shows that Pembrolizumab, when combined with chemotherapy, can improve survival rates in patients with advanced non-small cell lung cancer. In one study, patients receiving this combination had a 12-month survival rate of 69.2%, compared to 49.4% for those receiving chemotherapy alone.12345
Is the combination of pembrolizumab and chemotherapy safe for lung cancer patients?
How is the drug pembrolizumab plus chemotherapy different from other treatments for lung cancer?
Eligibility Criteria
This trial is for adults with Stage IV NSCLC, who are in good physical condition (ECOG 0 or 1) and have a confirmed diagnosis. Participants can be HIV-positive if their virus is well controlled on ART, and those with hepatitis B must be on antiviral therapy with an undetectable viral load.Inclusion Criteria
My HIV is well controlled with antiretroviral therapy.
My lung cancer is confirmed to be stage IV NSCLC.
I am HBsAg positive but have been on HBV therapy for 4 weeks with an undetectable viral load.
See 2 more
Exclusion Criteria
I had a heart or leg artery bypass surgery in the last 6 months.
I have not had a live vaccine in the last 30 days.
I have active brain metastases or cancer in my brain's lining.
See 28 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive pembrolizumab with or without chemotherapy, and potentially HER3-DXd, for up to 35 cycles (~2 years)
Up to 2 years
Every 3 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 5 years
Treatment Details
Interventions
- Carboplatin (Chemotherapy)
- Paclitaxel (Chemotherapy)
- Pembrolizumab (Checkpoint Inhibitor)
- Pemetrexed (Chemotherapy)
Trial OverviewThe study tests the effectiveness of adding HER3-DXd to pembrolizumab, with or without chemotherapy drugs like Paclitaxel, Pemetrexed, Nab-paclitaxel, and Carboplatin in treating advanced NSCLC. It aims to assess safety and how well these combinations work.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Pembrolizumab and HER3-DXdExperimental Treatment2 Interventions
Pembrolizumab will be administered as a 200mg IV infusion on Day 1 Q3W for up to 35 cycles (\~ 2 years). HER3-Dxd will be administered as 5.6mg/kg IV infusion on Day 1 Q3W until discontinuation criteria is met.
Group II: Pembrolizumab and ChemotherapyActive Control5 Interventions
Pembrolizumab will be administered as a 200mg IV infusion on Day 1 of every three weeks (Q3W) for up to 35 cycles (\~ 2 years). The doublet platinum-based chemotherapy treatments used in this substudy are standard-of care regimens for squamous (paclitaxel/Nab-paclitaxel and carboplatin) and nonsquamous (pemetrexed and carboplatin) NSCLC. Pemetrexed is administered as a 500mg/m\^2 IV infusion Q3W until discontinuation criterion is met. Nab-paclitaxel will be administered as a 100mg/m\^2 IV infusion on Days 1, 8, and 15 Q3W for 4 cycles. Paclitaxel will be administered as a 200 mg/m\^2 IV infusion on Day 1 Q3W for up to 4 cycles. Carboplatin will be administered as an IV infusion area under the time x concentration curve (AUC) for 4 cycles as per local practice and labels. The dose will be AUC5 or 6 mg/mL•min Q3W and will not exceed 900mg.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MedStar Franklin Square Medical Center ( Site 0033)Baltimore, MD
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLCLead Sponsor
Daiichi SankyoIndustry Sponsor
References
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. [2022]Despite recent advances in the treatment of advanced non-small-cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.
Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. [2022]In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs).
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
Combo Therapy for Lung Cancer Extends Survival. [2019]The PD-1 inhibitor pembrolizumab in combination with chemotherapy may be an effective therapy for patients with newly diagnosed advanced non-squamous non-small cell lung cancer. In a clinical trial, patients who received the combination had an estimated 12-month overall survival rate of 69.2%, compared with 49.4% in patients who received chemotherapy alone.
Pembrolizumab for the treatment of nonsmall cell lung cancer: Current status and future directions. [2020]The development of inhibitors of immune checkpoints has revolutionized the treatment for a subset of patients with advanced nonsmall cell lung cancer (NSCLC), resulting in promising clinical outcomes and durable responses. Pembrolizumab, a humanized anti-programmed cell death-1 (PD-1) antibody, has been approved as a first-line treatment for patients with advanced NSCLC with PD-L1 expression of ≥50% and as a second-line treatment for PD-L1 expression of ≥1%. Pembrolizumab in combination with standard chemotherapy has shown better clinical outcomes than chemotherapy as a first-line therapy in patients with advanced NSCLC without targetable mutations, regardless of PD-L1 expression. In this review, we summarized the current indications of pembrolizumab for NSCLC, briefly described immune-relevant pneumonitis and discussed potential biomarkers to predict clinical efficacy.
Effectiveness and safety of pembrolizumab monotherapy in patients with locally advanced or metastatic non-small-cell lung cancer. [2022]Immunotherapy has become a standard treatment for lung cancer; the objective of this study was to evaluate the effectiveness, safety of pembrolizumab monotherapy in patients with advanced or metastatic non-small-cell lung cancer used in real-world clinical practice.
Pembrolizumab. [2022]The development of the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab and its approval in 2011 for the treatment of metastatic melanoma has heralded a new era in immuno-oncology. Subsequently, novel agents against the programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis have shown significant activity in melanoma and a variety of other tumor types. Pembrolizumab was the first anti-PD-1 antibody to be approved by the US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma with disease progression following ipilimumab, and if BRAF (V600) mutation positive, a BRAF inhibitor. Pembrolizumab has also received breakthrough status for the treatment of EGFR mutation-negative, ALK rearrangement-negative non-small cell lung cancer (NSCLC) that has progressed on or following platinum-based chemotherapy. There remain a number of pivotal trials in progress to further evaluate the optimal use of pembrolizumab alone and in combination for melanoma, NSCLC, and other tumor types. In this article, we review the efficacy and toxicity profile of pembrolizumab and evaluate its future development.
Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. [2021]The safety of pembrolizumab monotherapy in treatment-naïve non-small cell lung cancer (NSCLC) patients with high programed death-ligand 1 (PD-L1) expression and pre-existing interstitial lung disease (ILD) has not yet been determined. Here, we aimed to evaluate the prognosis, efficacy and safety associated with pembrolizumab in such settings.
Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.
Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science.
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.
Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC. [2022]Pembrolizumab plus chemotherapy significantly improved outcomes over chemotherapy alone as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC) in phase 3 international trials. In the phase 1 KEYNOTE-011 study (parts B and C), we evaluated the safety/activity of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC.
Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. [2022]Pembrolizumab is a humanized monoclonal antibody which serves to enhance the antitumor immune response by targeting programmed cell death 1 receptor. The use of pembrolizumab plus carboplatin/pemetrexed combination therapy results in improvement in overall survival and progression-free survival rates for non-small cell lung cancer (NSCLC) patients as compared to chemotherapy alone. However, numerous immune-mediated toxicities of pembrolizumab have been reported.