Ramucirumab + Pembrolizumab vs Chemotherapy for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+562 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Southwest Oncology Group
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase III trial compares the effect of the combination of ramucirumab and pembrolizumab versus standard of care chemotherapy for the treatment of non-small cell lung cancer that is stage IV or that has come back after a period of improvement (recurrent). Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out if giving ramucirumab with pembrolizumab is more effective at treating patients with stage IV or recurrent non-small cell lung cancer than standard chemotherapy.
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 team or your doctor.
What data supports the effectiveness of the drug combination of Ramucirumab and Pembrolizumab for non-small cell lung cancer?
Research shows that Pembrolizumab, when combined with chemotherapy, is effective in treating advanced non-small cell lung cancer, improving survival rates and reducing disease progression. Additionally, Pembrolizumab alone has been shown to improve survival in patients with high PD-L1 expression, suggesting its potential effectiveness in combination with other treatments like Ramucirumab.
12345Is the combination of Ramucirumab and Pembrolizumab safe for humans?
Pembrolizumab (Keytruda) has been used in various cancer treatments and is generally considered less toxic than traditional chemotherapy, but it can cause side effects like pneumonitis (lung inflammation), fatigue, and nausea. Immune-related side effects such as colitis (inflammation of the colon), hepatitis (liver inflammation), and thyroid disorders have also been reported. While these side effects can be serious, the benefits of treatment often outweigh the risks for life-threatening conditions.
16789How is the drug combination of Ramucirumab and Pembrolizumab different from other treatments for non-small cell lung cancer?
This treatment combines Ramucirumab, which targets blood vessels to stop tumor growth, with Pembrolizumab, an immunotherapy that helps the immune system attack cancer cells, offering a unique approach compared to traditional chemotherapy alone.
1391011Eligibility Criteria
This trial is for adults with stage IV or recurrent non-small cell lung cancer who've seen their disease progress after anti-PD-1/PD-L1 therapy and platinum-based chemotherapy. They should have had a positive response to previous immunotherapy, be in fair health (Zubrod status 0-2), and able to receive the study drugs safely. Those with certain mutations must have tried FDA-approved targeted therapies.Inclusion Criteria
My lung cancer is confirmed to be stage IV or has come back.
I can take care of myself and am up and about more than 50% of my waking hours.
I am 18 years old or older.
Exclusion Criteria
I have not had more than one type of immunotherapy for my advanced or recurrent cancer.
Participant Groups
The Pragmatica-Lung Study is testing if combining ramucirumab (a drug that may stop blood vessel growth in tumors) with pembrolizumab (an immune system booster) works better than standard chemotherapy alone for advanced or returning non-small cell lung cancer.
2Treatment groups
Experimental Treatment
Active Control
Group I: ARM B (ramucirumab, pembrolizumab)Experimental Treatment2 Interventions
Patients receive ramucirumab IV and pembrolizumab IV on study.
Group II: ARM A (standard of care chemotherapy)Active Control1 Intervention
Patients receive chemotherapy per standard of care on study.
Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Chemotherapy for:
- Breast cancer
- Metastatic breast cancer
- Various other cancers
🇺🇸 Approved in United States as Chemotherapy for:
- Breast cancer
- Metastatic breast cancer
- Various other cancers
🇨🇦 Approved in Canada as Chemotherapy for:
- Breast cancer
- Metastatic breast cancer
- Various other cancers
🇯🇵 Approved in Japan as Chemotherapy for:
- Breast cancer
- Metastatic breast cancer
- Various other cancers
🇨🇳 Approved in China as Chemotherapy for:
- Breast cancer
- Metastatic breast cancer
- Various other cancers
🇨🇭 Approved in Switzerland as Chemotherapy for:
- Breast cancer
- Metastatic breast cancer
- Various other cancers
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of New Mexico Cancer CenterAlbuquerque, NM
Miami Valley Hospital SouthCenterville, OH
Kaiser Permanente-Baldwin ParkBaldwin Park, CA
Freeman Physician Group of PittsburgPittsburg, KS
More Trial Locations
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Who is running the clinical trial?
Southwest Oncology GroupLead Sponsor
SWOG Cancer Research NetworkLead Sponsor
Eli Lilly and CompanyIndustry Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
National Cancer Institute (NCI)Collaborator
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression ≥50. [2021]Pembrolizumab plus chemotherapy is currently used in the first-line treatment of advanced non-small-cell lung cancer without EGFR mutations or ALK rearrangements, regardless of PD-L1 expression status. A study comparing chemotherapy plus pembrolizumab versus pembrolizumab alone has never been performed in patients with PD-L1 ≥50%. The aim of this trial is to perform such a comparison as first-line treatment in patients not eligible for locally advanced treatment who have expression of PD-L1 on ≥50% of tumor cells. The expected results are a reduction in the risk of early progression. A higher objective tumor response is also expected with the combination of chemotherapy and pembrolizumab compared with pembrolizumab alone. The study will allow a direct comparison of the proportion of patients who derive long-term benefit from the treatment. Clinical trial number: EudraCT (2020-002626-86); ClinicalTrials.gov (NCT04547504).
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.
Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. [2022]A systematic review and network meta-analysis were conducted to evaluate the efficacy of pembrolizumab + pemetrexed + platinum relative to other regimens in metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC).
Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. [2018]This review describes trials evaluating the monoclonal antibody pembrolizumab (an immunotherapy that blocks the interaction between programmed death-1 and programmed death-ligand 1 and 2 [PD-L1/PD-L2]) as first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the Phase III KEYNOTE-024 study, pembrolizumab monotherapy significantly improved progression-free survival (primary end point) and overall survival, and was associated with fewer adverse events compared with platinum-based chemotherapy in patients with NSCLC with PD-L1 expression on ≥50% of tumor cells. In cohort G of the Phase I/II KEYNOTE-021 study, pembrolizumab plus pemetrexed and carboplatin significantly improved objective response rate (primary end point) and progression-free survival versus pemetrexed and carboplatin alone, and had manageable toxicity in patients with nonsquamous NSCLC. These results have changed first-line management of advanced NSCLC.
New Approved Use for Keytruda. [2022]Pembrolizumab (Keytruda) is now approved as a single agent to treat advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient in those whose disease has progressed following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
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).
PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. [2023]There are currently three first-line immunotherapy options used as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand 1 (PD-L1) expression (≥50%). This manuscript aims to evaluate the available data on atezolizumab (AT), cemiplimab (CEMI), and pembrolizumab (PEMBRO) and to study the results obtained during pivotal trials, especially regarding patient subgroups.
Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. [2022]Pembrolizumab is a standard-of-care for advanced non-small-cell lung cancer (NSCLC). We assessed pembrolizumab as adjuvant therapy for completely resected stage IB-IIIA NSCLC.