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

Trial Summary

What is the purpose of this trial?

Evaluate frequency of adverse events that lead to chemotherapy discontinuation in vulnerable older adults with recurrent/metastatic PD-L1 TPS\<50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy.

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.

What data supports the effectiveness of the treatment Reduced Chemotherapy + Immunotherapy for Lung Cancer?

Research shows that combining immunotherapy with chemotherapy can improve and extend the response in patients with advanced lung cancer by enhancing the immune system's ability to fight the cancer and reducing the tumor's ability to hide from the immune system. Adjusting the dose of chemotherapy can also help reduce side effects while maintaining the effectiveness of the treatment. ^{1 2 3 4 5}

Is reduced chemotherapy plus immunotherapy safe for humans?

Reduced chemotherapy combined with immunotherapy has been studied for safety, showing that while it can be effective, it may cause immune-related side effects like autoimmune diseases and lung issues. These side effects are generally rare but can be serious, so careful management is important. ^{6 7 8 9 10}

How is the Reduced Chemotherapy + Immunotherapy treatment for lung cancer different from other treatments?

This treatment combines a reduced dose of chemotherapy with immunotherapy, which helps the immune system recognize and attack cancer cells more effectively. Unlike traditional chemotherapy alone, this approach aims to enhance the immune response while minimizing side effects by using lower chemotherapy doses. ^{11 12 13 14 15}

Research Team

Jonathan Berkman, MD

Principal Investigator

Virginia Commonwealth University

Eligibility Criteria

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%

I can care for myself but may not be able to do heavy physical work.

ANC ≥ 1,000/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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

The Value of Hope: Patients' and Physicians' Preferences for Survival in Advanced Non-Small Cell Lung Cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Combining Immunotherapy and Chemotherapy for Non-Small Cell Lung Cancer. [2020]

3. United States 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. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[TTF-1-negative lung adenocarcinoma: special features of systemic treatment]. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Adjusting the dose of traditional drugs combined with immunotherapy: reshaping the immune microenvironment in lung cancer. [2023]

6. France pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Management of pulmonary toxicity associated with immune checkpoint inhibitors. [2022]

8. United States 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. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Lung cancer: potential targets for immunotherapy. [2014]

12. Hungary pubmed.ncbi.nlm.nih.gov

[Immunotherapy of lung cancer]. [2020]

13. France pubmed.ncbi.nlm.nih.gov

["Treatment of lung cancer with immune checkpoints inhibitors"]. [2021]

14. Scotland pubmed.ncbi.nlm.nih.gov

Molecular basis and rationale for combining immune checkpoint inhibitors with chemotherapy in non-small cell lung cancer. [2020]

15. United States pubmed.ncbi.nlm.nih.gov

Using Immune Checkpoint Inhibitors in Lung Cancer. [2021]