Immunotherapy + Radiation for Advanced Non-Small Cell Lung Cancer

(IRRADIATE-Lung Trial)

Overseen By Vamsidhar Velcheti, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, 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: 11

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding low-dose radiation to the standard treatment of pembrolizumab (a type of immunotherapy) and chemotherapy can enhance outcomes for people with advanced non-small cell lung cancer (NSCLC). It focuses on those whose cancer has spread or returned. Participants must have metastatic NSCLC and not have received previous systemic therapy. The study aims to improve treatment effectiveness by combining therapies. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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 systemic steroid therapy or any form of immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

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

Research has shown that pembrolizumab, when combined with chemotherapy, is generally well-tolerated by patients with advanced non-small cell lung cancer (NSCLC). Many studies have demonstrated significant benefits from this combination. Specifically, data from several trials confirm pembrolizumab's safety and effectiveness in treating advanced NSCLC.

Additionally, research examining pembrolizumab with radiation therapy found this combination safe and potentially effective for patients. While all treatments can have side effects, existing research suggests that pembrolizumab, along with chemotherapy and radiation, remains a safe option, especially with close monitoring for adverse effects.

Overall, previous studies have shown promising safety results when combining pembrolizumab with chemotherapy and low-dose radiation. This supports its use in treating advanced lung cancer and offers hope for those considering joining clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining immunotherapy with radiation for advanced non-small cell lung cancer (NSCLC) because it offers a new approach to tackling the disease. While standard treatments usually involve chemotherapy alone, this method uses pembrolizumab, an immunotherapy drug, alongside radiation. Pembrolizumab works by boosting the body's immune system to better detect and attack cancer cells. The addition of radiation may enhance this effect, potentially leading to more effective tumor reduction. This combination could provide a more powerful treatment option for patients with advanced NSCLC.

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

Research has shown that pembrolizumab, when combined with chemotherapy, greatly benefits people with advanced non-small cell lung cancer (NSCLC). Specifically, studies found that about 19% of patients lived for five years after receiving this treatment, a significant improvement over chemotherapy alone. In this trial, participants will receive radiation alongside chemotherapy and pembrolizumab. Combining pembrolizumab with radiation has strengthened the body's immune response against tumors. Several trials have confirmed pembrolizumab's effectiveness in treating advanced NSCLC. These findings suggest that adding radiation could enhance the treatment's success. ^{2 3 6 7 8}

Who Is on the Research Team?

Vamsidhar Velcheti, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults with advanced Stage IV NSCLC who haven't had systemic therapy before. Participants need at least one measurable lung lesion outside the radiation field, must not be pregnant or breastfeeding, and agree to use contraception. They can't join if they have active infections, other cancers needing treatment, certain autoimmune diseases, a history of severe allergies to pembrolizumab components, or are on immunosuppressants.

Inclusion Criteria

My recent tests show my organs are functioning well.

I have at least 2 large, measurable cancer spread sites, with one not treated by radiation.

You have a disease that can be measured using a specific medical guideline.

Exclusion Criteria

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have been diagnosed with HIV.

I have not had radiation in the same area where I am now planning to have it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive non-ablative focal radiation therapy to up to five distinct metastatic subsites

1 week

5 visits (in-person)

Treatment

Participants receive chemotherapy with pembrolizumab for up to 6 cycles

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Pembrolizumab
• Radiation

Trial Overview

The study tests whether low dose radiation alongside standard pembrolizumab (an immunotherapy drug) and chemotherapy improves outcomes in advanced lung cancer patients. It's designed for those with untreated Stage IV NSCLC to see if symptom control through radiation can boost the effectiveness of these treatments.

How Is the Trial Designed?

Group I: Untreated Patients With Stage IV NSCLC Experimental Treatment 3 Interventions

Participants will receive radiation in concert with starting chemotherapy with pembrolizumab for up to 6 cycles (18 weeks), followed by continued treatment with pembrolizumab (standard of care). Patients will be followed for 1 year following the completion of the core study period of 6 cycles.

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

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

In a trial involving 25 patients with locally advanced non-small-cell lung cancer (LA-NSCLC) and a PD-L1 tumor proportion score of ≥50%, the combination of pembrolizumab and risk-adapted radiotherapy achieved a 1-year progression-free survival rate of 76%, indicating strong efficacy without the use of chemotherapy.

The treatment was well-tolerated, with only 8% of patients experiencing grade 3 adverse events like colitis and esophagitis, and no higher-grade treatment-related adverse events reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Personalized Radioimmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial. Ohri, N., Jolly, S., Cooper, BT., et al.[2023]

A case study of a 52-year-old man with HIV and lung adenocarcinoma showed that combining pembrolizumab with stereotactic body radiotherapy led to serious immune-related adverse events, including massive pericardial effusion and interstitial pneumonia.

Despite initial treatment with pembrolizumab and radiotherapy, the patient's condition worsened, highlighting the need for caution and further clinical trials to assess the safety and efficacy of this combination therapy in HIV-infected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report. Li, D., He, C., Xia, Y., et al.[2018]

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