Trial Summary
What is the purpose of this trial?This pilot study is configured as a non-inferiority comparison of Performance Status 2 patients with Performance Status 0-1 patients, with the goal of demonstrating non-inferiority in terms of efficacy (progression-free survival, overall survival) and safety (rates of adverse events, quality of life) when treating Performance Status 2 patients with the same first-line immunotherapy-based regimen as Performance Status 0-1 patients.
Is the drug combination of Carboplatin, Nab paclitaxel, Paclitaxel, Pembrolizumab, and Pemetrexed promising for treating non-small cell lung cancer?Yes, this drug combination is promising for treating non-small cell lung cancer. Studies show that using Pembrolizumab with chemotherapy, including Carboplatin and Pemetrexed, is now a standard first-line treatment for advanced cases. This combination has been effective in real-life settings, making it a strong option for patients.5791011
What safety data is available for chemo/immunotherapy in non-small cell lung cancer?Safety data for the treatment of non-small cell lung cancer with chemo/immunotherapy, including drugs like pemetrexed, carboplatin, and pembrolizumab, is available from various studies. Pemetrexed, when combined with cisplatin, has been associated with adverse events such as neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. Pembrolizumab combined with chemotherapy is now a standard first-line treatment for advanced non-squamous non-small cell lung cancer, and its safety has been assessed in real-life studies. Additionally, a phase II trial of pembrolizumab as neoadjuvant therapy in resectable non-small cell lung cancer has conducted an interim safety analysis. Patients receiving pemetrexed are advised to take folic acid, vitamin B12, and corticosteroids to mitigate severe toxicities and skin rashes.234810
What data supports the idea that Chemo/Immunotherapy for Non-Small Cell Lung Cancer is an effective treatment?The available research shows that combining pembrolizumab with chemotherapy drugs like carboplatin and pemetrexed is effective for treating advanced non-small cell lung cancer. One study highlights that this combination is now a standard first-line treatment, meaning it's often the first choice for doctors. Another study compared this combination to using carboplatin and pemetrexed alone and found promising results, suggesting that adding pembrolizumab improves outcomes. These findings support the idea that this chemo/immunotherapy approach is effective for this type of lung cancer.168910
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications for an active autoimmune disease or have a history of pneumonitis requiring systemic corticosteroids, you may be excluded from the trial. It's best to discuss your specific medications with the trial team.
Eligibility Criteria
This trial is for adults with non-small cell lung cancer that's metastatic or can't be surgically removed, and who haven't had chemo or immunotherapy before. They should have a life expectancy over 3 months, normal organ/marrow function, and no history of certain conditions like pneumonitis treated with steroids.Inclusion Criteria
I am 18 years old or older.
My blood tests show normal white blood cell and platelet counts.
My lung cancer cannot be removed by surgery and has no cure with standard treatments.
Exclusion Criteria
I have an autoimmune disease treated within the last 2 years.
I have had lung inflammation treated with steroids.
I do not have any severe illnesses or social situations that would stop me from following the study's requirements.
My lung cancer has a specific mutation that requires targeted therapy.
Treatment Details
The study tests if patients with lower performance status (weaker condition) do as well on first-line immunotherapy-based treatments as those in better condition. It involves drugs like Pembrolizumab and chemotherapy agents, along with quality of life assessments.
2Treatment groups
Experimental Treatment
Group I: Performance Status 2 ParticipantsExperimental Treatment8 Interventions
ALL study participants will receive pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle.
Participants with predictive biomarker PD-L1 greater than or equal to 50%: Participants will not receive any other drugs besides pembrolizumab.
Participants with Non-squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will ALSO receive:
- Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles.
PLUS
- Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.
Participants with Squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will also receive:
* Carboplatin AUC 5 IV on day 1 of each 3-week cycle for 4 cycles. PLUS
* Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles. OR
* Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles
Group II: Performance Status 0-1 ParticipantsExperimental Treatment8 Interventions
ALL study participants will receive pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle.
Participants with predictive biomarker PD-L1 greater than or equal to 50%: Participants will not receive any other drugs besides pembrolizumab.
Participants with Non-squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will ALSO receive:
- Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles.
PLUS
- Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.
Participants with Squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will also receive:
* Carboplatin AUC 5 IV on day 1 of each 3-week cycle for 4 cycles. PLUS
* Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles. OR
* Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles
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:
Wake Forest Baptist Comprehensive Cancer CenterWinston-Salem, NC
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Who is running the clinical trial?
Wake Forest University Health SciencesLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. [2017]Pemetrexed (Alimta) is a novel multitargeted antifolate that has activity against non-small-cell lung cancer (NSCLC). As a single agent, the response rate is 16%-23%. As second-line therapy, it has a 5% and 14% response rate with pemetrexed in NSCLC patients who have had prior cisplatin or nonplatinum chemotherapy, respectively. Pemetrexed combined with cisplatin has a response rate of 38.9%-44.8%, with a median survival of 8.9-10.9 months. Pemetrexed plus gemcitabine in NSCLC has a response rate of less than 25%. The major toxicity associated with pemetrexed is neutropenia, which may be reduced with vitamin B12 and folate nutritional supplement. Additional studies with pemetrexed in combination with other agents are needed for the treatment of NSCLC patients.
FDA drug approval summaries: pemetrexed (Alimta). [2022]The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta; Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol; Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit.
Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]Pemetrexed has established efficacy, and is the backbone for chemotherapy in patients with malignant pleural mesothelioma (MPM). An International Expanded Access Program provided >3000 mesothelioma patients with access to single-agent pemetrexed or pemetrexed plus platinum analogs (cisplatin or carboplatin) in 13 countries. In this article, we report the safety and efficacy data of MPM patients who were treated with single-agent pemetrexed (n = 812).
Pemetrexed disodium for the treatment of NSCLC: an update. [2017]Pemetrexed disodium is a multitargeted antifolate cytotoxic chemotherapy agent approved by the U.S. Food and Drug Administration (FDA) initially for the treatment of malignant pleural mesothelioma, and in August 2004 for second-line treatment of non-small cell lung cancer (NSCLC). In September 2008, the FDA also approved pemetrexed and cisplatin as first-line therapy for NSCLC. Pemetrexed is also no longer recommended for treatment of NSCLC with squamous cell carcinoma histology. Pemetrexed is currently being tested in clinical trials as part of second-line combination, first-line, adjuvant and maintenance therapies.
Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. [2021]This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC).
A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer. [2023]Randomized phase II and III studies showed the promising results of the combination of carboplatin/pemetrexed with pembrolizumab in non-squamous non-small cell lung cancer patients. Patients with brain metastases were excluded from the phase II study. After FDA approval, this regimen was adopted early at our institution, including a use in patients with brain metastases. We report real-world use of this regimen in a single medical center.
Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial. [2021]We report the final results of the phase 3 IMpower132 study evaluating atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) in patients with nonsquamous NSCLC.
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.
An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. [2021]Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin.
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.
Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). [2023]Pemetrexed-based immunochemotherapy represents an established standard of care as first line treatment for non-oncogenic driven metastatic non-small cell lung adenocarcinoma (NSCLC/ADC). However, retrospective analyses revealed better outcomes for pemetrexed-free regimens compared to pemetrexed-containing regimens in patients with thyroid transcription factor 1 (TTF-1) negative NSCLC/ADC. The multicenter, phase II, randomized, open-label ANTELOPE trial evaluates whether atezolizumab, carboplatin and nab-paclitaxel is superior to pembrolizumab, cis-/carboplatin and pemetrexed in TTF-1 negative NSCLC/ADC.