Chemo/Immunotherapy for Non-Small Cell Lung Cancer

Overseen By Principal Investigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Immunosuppressive drugs

Disqualifiers: Autoimmune disease, Pneumonitis, Cardiac illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy and immunotherapy for individuals with non-small cell lung cancer (NSCLC) that cannot be surgically removed or has metastasized. The researchers aim to determine if a specific treatment approach is as effective and safe for less active patients (Performance Status 2) as it is for more active patients (Performance Status 0-1). Participants will receive drugs such as pembrolizumab (an immunotherapy) and carboplatin (a chemotherapy), tailored to their specific lung cancer type and certain biomarkers. Suitable candidates have NSCLC that has not been treated with chemotherapy or immunotherapy for non-curative purposes and experience significant limitations in daily activities due to their condition. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 treatment, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments under study are generally safe. Long-term studies have demonstrated that pembrolizumab, when combined with chemotherapy, helps patients live longer and is usually well-tolerated. Side effects are noted but generally align with expectations for this type of treatment.

Carboplatin, often used to treat lung cancer, has been extensively studied. It has a predictable safety profile, with known side effects that can often be well-managed.

Pemetrexed, used for non-small cell lung cancer, is considered safe, with studies indicating it is generally well-tolerated. Similarly, research has shown that paclitaxel and nab-paclitaxel improve patient outcomes, with manageable side effects.

These treatments are being tested in a Phase 2 trial, indicating they have already demonstrated some level of safety in earlier studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for non-small cell lung cancer because it combines immunotherapy with chemotherapy in a personalized approach. Pembrolizumab, an immunotherapy, is used to boost the immune system's ability to fight cancer by targeting the PD-L1 biomarker. Unlike the standard of care, which often involves chemotherapy alone, this treatment tailors the combination of drugs based on the cancer's subtype and PD-L1 levels. This personalized approach aims to enhance treatment effectiveness and potentially improve outcomes for patients with different cancer profiles.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that pembrolizumab, administered to all participants in this trial, significantly improves survival rates for patients with non-small cell lung cancer (NSCLC), with about 19% of patients living for five years. In this trial, participants with a PD-L1 biomarker less than 50% will receive additional treatments based on their cancer subtype. For non-squamous NSCLC, participants will also receive carboplatin and pemetrexed. Studies demonstrate that carboplatin is effective in combination treatments, while pemetrexed is particularly effective for non-squamous NSCLC, consistently delivering positive results in clinical trials. For squamous NSCLC, participants will receive carboplatin and either paclitaxel or nab-paclitaxel. Paclitaxel, often used in combination therapies, has achieved response rates of up to 30% and is a standard part of NSCLC treatment plans. Nab-paclitaxel, when combined with carboplatin, has extended the time patients live without their disease worsening and improved overall survival, especially in those who have had previous chemotherapy. Together, these treatments provide a strong first-line approach for managing NSCLC. ^{1 2 4 6 7}

Who Is on the Research Team?

Thomas Lycan

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

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

My blood tests show normal white blood cell and platelet counts.

I haven't had chemotherapy or immunotherapy for my cancer, except possibly for early-stage treatment.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab every 3 weeks, with additional chemotherapy drugs based on subtype and biomarker status, for 4 cycles

12 weeks

4 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Nab paclitaxel
• Paclitaxel
• Pembrolizumab
• Pemetrexed

Trial Overview 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.

How Is the Trial Designed?

Group I: Performance Status 2 Participants Experimental Treatment 8 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 Participants Experimental Treatment 8 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

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pemetrexed disodium is an FDA-approved chemotherapy drug effective for treating malignant pleural mesothelioma and non-small cell lung cancer (NSCLC), particularly in combination with cisplatin as a first-line therapy.

Current guidelines indicate that pemetrexed is not recommended for NSCLC with squamous cell carcinoma histology, and it is being explored in various clinical trials for additional treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed disodium for the treatment of NSCLC: an update. Hsu, JY., Wakelee, H.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study involving 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[2015]

The phase 3 IMpower132 study demonstrated that the combination of atezolizumab with carboplatin or cisplatin plus pemetrexed (APP) significantly improved progression-free survival (PFS) in patients with stage IV nonsquamous NSCLC, with a median PFS of 7.6 months compared to 5.2 months for the standard chemotherapy (PP).

While overall survival (OS) showed a numerical improvement for the APP group (median OS of 17.5 months vs. 13.6 months for PP), this difference was not statistically significant, indicating that APP has a manageable safety profile with no new safety concerns, although it did have a higher incidence of grade 3 or 4 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial. Nishio, M., Barlesi, F., West, H., et al.[2021]

Pemetrexed, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

The ANTELOPE trial is a phase II study comparing the efficacy of a pemetrexed-free regimen (atezolizumab, carboplatin, and nab-paclitaxel) against a pemetrexed-based regimen (pembrolizumab, cis-/carboplatin, and pemetrexed) in treating TTF-1 negative non-small cell lung adenocarcinoma (NSCLC/ADC).

This trial aims to enroll 136 participants across 30 sites in Germany, focusing on overall survival as the primary endpoint, which will help determine the best treatment approach for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Frost, N., Bleckmann, A., Griesinger, F., et al.[2023]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a study involving 180 patients with advanced non-small cell lung cancer (NSCLC), pemetrexed-carboplatin did not show superior efficacy compared to paclitaxel-carboplatin, with similar progression-free survival (PFS) rates and overall survival after a median follow-up of 17 months.

While both treatment regimens had comparable overall toxicities, the paclitaxel-carboplatin group experienced higher rates of alopecia and peripheral neuropathy, indicating a difference in side effects between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Yadav, A., Malik, PS., Khurana, S., et al.[2021]

The combination of carboplatin and dose-dense pemetrexed with involved field radiotherapy is feasible for treating locally advanced and oligometastatic non-small cell lung cancer (NSCLC), as shown in a phase I study with 18 enrolled patients.

Despite some dose-limiting toxicities observed, the treatment resulted in a median survival time of 28.6 months, with 13 out of 16 evaluable patients showing a local regional response, indicating promising efficacy for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. Shen, X., Denittis, A., Werner-Wasik, M., et al.[2021]

Pemetrexed (Alimta) shows a response rate of 16%-23% as a single agent for non-small-cell lung cancer (NSCLC) and a higher response rate of 38.9%-44.8% when combined with cisplatin, leading to a median survival of 8.9-10.9 months.

The main side effect of pemetrexed is neutropenia, but this can be mitigated with vitamin B12 and folate supplements, highlighting the importance of supportive care in enhancing treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. Ettinger, DS.[2017]

In a real-world study of 54 patients with advanced non-squamous non-small cell lung cancer, the combination of carboplatin, pemetrexed, and pembrolizumab showed a higher disease control rate (86.7%) compared to carboplatin and pemetrexed alone (54%).

Patients with brain metastases treated with the combination therapy had a significantly lower progression rate (33.3%) compared to those receiving only carboplatin and pemetrexed (91.7%), indicating that this regimen may be particularly effective for this challenging patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Afzal, MZ., Dragnev, K., Shirai, K.[2023]

Citations

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