Reduced Chemotherapy + Immunotherapy for Lung Cancer

Overseen By Massey IIT Research Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, Interstitial lung disease, 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: 3

Duration: Up to 2 years

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treat lung cancer using a combination of reduced chemotherapy and immunotherapy, a type of biological therapy. The goal is to determine how often older adults with certain types of lung cancer must stop chemotherapy due to side effects. It targets individuals with advanced non-small cell lung cancer (NSCLC) that has recurred or spread and lacks specific genetic changes for targeted treatments. Candidates should have stage IV or recurrent lung cancer and should not have received treatment for the cancer in its current state. This trial may suit those diagnosed with this type of lung cancer and experiencing advancing symptoms. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings in lung cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medication, you may need to adjust your dosage or stop, unless it's a low dose or a short course.

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

Research has shown that combining pembrolizumab with chemotherapy is generally well-tolerated by people with non-small cell lung cancer (NSCLC). Studies have demonstrated that this treatment can significantly improve survival rates compared to chemotherapy alone.

One study found that using pembrolizumab with chemotherapy more than doubled the average survival time for patients with advanced NSCLC. Another study confirmed that combining carboplatin and (nab)paclitaxel with pembrolizumab is safe for both main types of NSCLC, leading to its approval as a first-choice treatment.

While these results are promising, every treatment can have side effects. This trial aims to determine if lowering the chemotherapy dose while using immunotherapy can reduce side effects, especially in older adults. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of reduced chemotherapy and immunotherapy for lung cancer because it aims to minimize chemotherapy's harsh side effects while boosting the body's immune response to cancer cells. Unlike standard treatments that rely heavily on full-dose chemotherapy, this approach uses a reduced dose of chemotherapy drugs like carboplatin and paclitaxel or pemetrexed, paired with the immunotherapy drug pembrolizumab. Pembrolizumab, an immune checkpoint inhibitor, helps the immune system recognize and attack cancer cells more effectively. This combination could potentially lead to better tolerability and improved outcomes for patients compared to traditional chemotherapy regimens.

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

Research has shown that pembrolizumab, a type of immunotherapy, combined with a reduced dose of chemotherapy, can help lung cancer patients live longer. In this trial, participants will receive this combination therapy, which significantly extends life, even for those with low levels of the protein PD-L1, known to influence cancer growth. Specifically, pembrolizumab with chemotherapy effectively shrinks or slows down tumors. Although side effects occur, they are generally not severe, making the treatment's safety manageable. This evidence supports the potential effectiveness of this treatment for patients with non-small cell lung cancer (NSCLC). ^{1 6 7 8 9}

Who Is on the Research Team?

Jonathan Berkman, MD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

This trial is for older adults with a specific type of lung cancer (NSCLC) that has spread and doesn't have much PD-L1 protein. They should be somewhat fit, not too sick from other diseases, able to understand the study, and haven't had certain treatments before. People who are very ill or have immune system problems can't join.

Inclusion Criteria

PD-L1 tumor proportion score (TPS) less than 50%

ANC ≥ 1,000/μL

Platelets ≥ 75,000/μL

Exclusion Criteria

Life expectancy of less than 3 months at the time of enrollment

Active autoimmune disease requiring systemic treatment in past 2 years

I am currently taking medication to suppress my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive reduced dose chemotherapy and immunotherapy. For squamous cell histology: Carboplatin and Paclitaxel every 21 days for 4 cycles, Pembrolizumab every 21 days up to 35 cycles. For non-squamous histology: Carboplatin and Pemetrexed every 21 days for 4 cycles, Pembrolizumab every 21 days up to 35 cycles.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival.

Up to 5 years

Quality of Life Assessment

Evaluate impact of the reduced dose combination therapy on quality of life using the EORTC QLQ-C30 questionnaire.

Up to 2 years

Baseline, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 9 Day 1, EOT Visit

What Are the Treatments Tested in This Trial?

Interventions

• Immunotherapy
• Reduced Dose of Chemotherapy

Trial Overview The study tests if giving a smaller dose of chemotherapy along with an immunotherapy drug causes fewer serious side effects in older or frail patients with advanced NSCLC that lacks high levels of PD-L1 protein.

How Is the Trial Designed?

Group I: Reduced Dose Combination Therapy Experimental Treatment 1 Intervention

Squamous cell histology: 1. Carboplatin AUC 3 every 21 days IV for 4 cycles 2. Paclitaxel 135 mg/m2 every 21 IV days for 4 cycles 3. Pembrolizumab 200 mg every 21 days IV until disease progression or unacceptable toxicity up to 35 cycles Non-squamous histology: 1. Carboplatin AUC 3 every 21 days IV for 4 cycles 2. Pemetrexed 375 mg/m2 every 21 IV days for 4 cycles 3. Pembrolizumab 200 mg every 21 days IV until disease progression or unacceptable toxicity up to 35 cycles

Immunotherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Various Immunotherapies for:

• Melanoma
• Non-Hodgkin lymphoma
• Chronic myelogenous leukemia (CML)
• Kidney cancer
• Breast cancer
• Prostate cancer

Approved in United States as Various Immunotherapies for:

• Melanoma
• Non-Hodgkin lymphoma
• Chronic myelogenous leukemia (CML)
• Kidney cancer
• Breast cancer
• Prostate cancer
• Bladder cancer

Approved in Canada as Various Immunotherapies for:

• Melanoma
• Non-Hodgkin lymphoma
• Chronic myelogenous leukemia (CML)
• Kidney cancer
• Breast cancer
• Prostate cancer

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Published Research Related to This Trial

In a study of 110 lung squamous cell carcinoma patients, reduced-dose chemotherapy combined with immunotherapy showed similar effectiveness to standard-dose chemotherapy, with an objective response rate of 85.19% compared to 71.43% in the standard-dose group.

The reduced-dose regimen resulted in significantly lower severe toxicities, particularly in thrombocytopenia, peripheral nerve damage, gastrointestinal reactions, and fatigue, making it a safer option for frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of reduced-dose chemotherapy plus immunotherapy in patients with lung squamous cell carcinoma: A real-world observational study. Ouyang, G., Liu, Y., Liu, J., et al.[2023]

Immune checkpoint inhibitors, specifically two anti-PD-1 monoclonal antibodies, have been approved for second-line treatment of advanced non-small-cell lung cancer (NSCLC), marking a significant shift in lung cancer therapy.

Ongoing clinical trials are exploring the use of these inhibitors in various combinations and stages of lung cancer, while research is also focused on identifying biomarkers to optimize their use, highlighting the need for improved efficacy and safety in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using Immune Checkpoint Inhibitors in Lung Cancer. Marrone, KA., Brahmer, JR.[2021]

Immunotherapy, particularly immune-checkpoint inhibitors, has become a standard treatment for various cancers, but it can lead to specific immune-related adverse events that require careful management.

Pulmonary toxicity, while not the most common side effect, is particularly dangerous and can be life-threatening, highlighting the need for awareness and guidelines to manage these potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of pulmonary toxicity associated with immune checkpoint inhibitors. Delaunay, M., Prévot, G., Collot, S., et al.[2022]

Immune checkpoint inhibitors, particularly anti-PD-1 and anti-PD-L1, have revolutionized lung cancer treatment, significantly improving survival rates in patients with metastatic non-small cell lung cancer (NSCLC), sometimes leading to prolonged survival without residual disease.

Durvalumab has shown to enhance survival in patients with locally advanced NSCLC following chemo-radiotherapy, while its impact on small cell lung cancer is more limited but still represents a breakthrough in improving survival for extensive-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

["Treatment of lung cancer with immune checkpoints inhibitors"]. Lamkhioued, M., Dupont, M., Leriche, P., et al.[2021]

Immunotherapy, particularly the use of immune checkpoint inhibitors like pembrolizumab and atezolizumab, has shown superior efficacy compared to chemotherapy alone in treating advanced non-small cell lung cancer (NSCLC), with these combinations now approved for first-line treatment.

Combining immune checkpoint inhibitors with chemotherapy enhances the immune system's ability to recognize and eliminate tumor cells while also reducing the immunosuppressive environment of tumors, which is crucial since only about 20% of patients respond to checkpoint blockade alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular basis and rationale for combining immune checkpoint inhibitors with chemotherapy in non-small cell lung cancer. Leonetti, A., Wever, B., Mazzaschi, G., et al.[2020]

The combination of platinum-based chemotherapy and immunotherapy is now the standard treatment for patients with metastatic non-small-cell lung cancer, regardless of their programmed death ligand 1 tumor proportion score.

Clinical trials have shown that this combination therapy can lead to improved and long-lasting responses by enhancing the immune system's ability to attack tumors and reducing the immunosuppressive environment that hinders immune detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Immunotherapy and Chemotherapy for Non-Small Cell Lung Cancer. Judd, J., Borghaei, H.[2020]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

Combining anti-PD-1 or anti-PD-L1 immunotherapy with platinum-based chemotherapy significantly improves outcomes for patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), based on a systematic review of 9 randomized studies.

While immune-mediated adverse events (AEs) and infusion reactions were more common with the combination therapy, there were no unexpected toxicities, indicating that the treatment is generally safe and manageable with appropriate monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. Hoffner, B., Leighl, NB., Davies, M.[2020]

Patients with advanced non-small cell lung cancer (NSCLC) prioritize the probability of long-term survival over expected survival, while physicians tend to value expected survival more highly, indicating a difference in perspectives on treatment outcomes.

Both patients and physicians agree that survival benefits are more important than treatment toxicities, highlighting the need for shared decision-making that considers patient values and priorities in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Value of Hope: Patients' and Physicians' Preferences for Survival in Advanced Non-Small Cell Lung Cancer. Hauber, B., Penrod, JR., Gebben, D., et al.[2022]

Immunotherapy, particularly with antibodies that block immune checkpoints, has shown promise in treating non-small-cell lung cancer (NSCLC), which is a major cause of cancer-related deaths.

There is a growing interest in combining immunotherapy with chemotherapy to enhance treatment effectiveness by inducing immunogenic cell death, highlighting the need for further clinical trials in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung cancer: potential targets for immunotherapy. Tartour, E., Zitvogel, L.[2014]

Anti-CTLA4 and anti-PD1/PD-L1 immunotherapies represent a significant shift in cancer treatment by enhancing the immune system's ability to fight tumors rather than directly targeting the tumor cells themselves.

These immunotherapies can lead to unique immune-related adverse events due to the activation of the immune system against normal tissues, necessitating changes in clinical management to address potential autoimmune reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Champiat, S., Michot, JM., Lambotte, O.[2019]

Biomarker-adjusted treatments have significantly improved survival rates in metastatic lung cancer patients, particularly those with actionable genomic alterations and those responding to checkpoint inhibitors (CPI).

For patients with lung adenocarcinoma and PD-L1 expression below 50%, chemotherapy is crucial, with ongoing trials investigating the potential survival benefits of taxane-based regimens compared to pemetrexed-based treatments, especially in patients negative for thyroid transcription factor 1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[TTF-1-negative lung adenocarcinoma: special features of systemic treatment]. Frost, N., Reck, M.[2023]

Immunotherapy has become a leading treatment for lung cancer, now approved for both first-line and second-line therapies, but its effectiveness varies among patients, highlighting the need for better combination strategies.

Recent studies indicate that optimizing drug dosages and timing, along with blocking resistance mechanisms, can enhance immune responses and reduce side effects, potentially improving the overall effectiveness of immunotherapy in lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjusting the dose of traditional drugs combined with immunotherapy: reshaping the immune microenvironment in lung cancer. Wang, L., Du, C., Jiang, B., et al.[2023]

Immune checkpoint inhibitors are now a standard treatment for advanced non-small cell lung cancer, either as monotherapy or in combination with chemotherapy, depending on the PD-L1 status of the tumor.

In small cell lung cancer, combining platinum-etoposide chemotherapy with PD-L1 inhibitors has become a new standard, although effective biomarkers for treatment response are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy of lung cancer]. Ostoros, G.[2020]

Continuing treatment with pembrolizumab (a checkpoint inhibitor) alongside next-line chemotherapy after disease progression in advanced non-small cell lung cancer (NSCLC) resulted in a median progression-free survival (PFS) of 5.1 months, which is significantly better than the historical control of 3 months with single-agent chemotherapy.

The study, involving 35 patients, also reported a median overall survival (OS) of 24.5 months, with manageable side effects such as fatigue and anemia, indicating that this treatment approach is both effective and safe for patients who previously benefited from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 trial of chemotherapy plus pembrolizumab in patients with advanced non-small cell lung cancer previously treated with a PD-1 or PD-L1 inhibitor: Big Ten Cancer Research Consortium BTCRC-LUN15-029. Salous, T., Shukla, NA., Althouse, SK., et al.[2023]

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Phase I/II Trial of Carboplatin, Nab-paclitaxel, and ... Carboplatin, nab-paclitaxel, and pembrolizumab are a safe and effective regimen for patients with both squamous and nonsquamous NSCLC.

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