Combination Immunotherapy for Lung Cancer

Recruiting at 349 trial locations

Overseen By Leon C. Hwang

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: SWOG Cancer Research Network

Must not be taking: Anti-CTLA4, Immunosuppressives

Disqualifiers: Organ transplant, Pneumonitis, Cardiac 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: 21

Duration: 2 years

82 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new combination of treatments for patients with advanced lung cancer. The treatments aim to boost the immune system's ability to fight cancer and prevent it from growing. The goal is to see if this combination can help patients live longer compared to standard treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received any systemic therapy, including chemotherapy or immunotherapy, within 21 days before starting the trial, and you cannot take certain medications like corticosteroids above a specific dose within 7 days prior. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination N-803 (ALT-803), Pembrolizumab, KEYTRUDA, MK-3475 for lung cancer?

Research shows that pembrolizumab, a part of this drug combination, is effective for treating non-small cell lung cancer (NSCLC). It has been approved by the FDA for improving survival in patients with advanced NSCLC, especially when tumors express a specific protein called PD-L1. ^{1 2 3 4 5}

Is the combination immunotherapy for lung cancer safe?

Pembrolizumab, a part of the combination immunotherapy, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, and nausea. Serious immune-related side effects, such as pneumonitis (lung inflammation) and type 1 diabetes, are rare but possible. ^{1 2 6 7 8}

What makes the combination immunotherapy with N-803 and pembrolizumab unique for lung cancer?

This combination therapy is unique because it combines N-803, which boosts the immune system's natural killer cells, with pembrolizumab, a PD-1 inhibitor that helps the immune system recognize and attack cancer cells. This dual approach may enhance the body's ability to fight lung cancer more effectively than using pembrolizumab alone. ^{1 2 4 5 9}

Research Team

John M Wrangle

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer that has spread and who have already tried certain FDA-approved therapies. They must have normal liver function or slightly elevated levels if they have liver metastases, no severe neurological issues from brain metastases, and should not be on high doses of steroids. Participants need to show progression after one line of anti-PD-1 or anti-PD-L1 therapy and be able to receive standard care treatments.

Inclusion Criteria

Your immune system has enough white blood cells called neutrophils.

My lung cancer has worsened after the latest treatment.

My brain or spinal metastases have been treated and are stable for over a week.

Exclusion Criteria

I am not pregnant or nursing and will use birth control during and 4 months after the study.

I do not need and am not planning to receive brain or spinal cord disease treatment during the first cycle of the study.

I am not planning to receive any other cancer treatments while on this study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV and nogapendekin alfa SC every 21 days for 2 years or standard of care treatment

2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• N-803 (ALT-803)
• Pembrolizumab

Trial Overview The study tests a combination immunotherapy treatment using N-803 (ALT-803) plus Pembrolizumab against the usual treatment for advanced non-small cell lung cancer. It aims to see if this combo can activate natural killer cells in the immune system to fight cancer more effectively than current methods.

Participant Groups

Group I: Arm B (pembrolizumab, nogapendekin alfa) Experimental Treatment 2 Interventions

Patients receive pembrolizumab IV over 30 minutes and nogapendekin alfa SC on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients then receive nogapendekin alfa SC on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (standard of care) Active Control 7 Interventions

Patients receive standard of care consisting of docetaxel IV over 30-60 minutes on day 1; gemcitabine IV over 30 minutes on days 1 and 8; pemetrexed IV over 10 minutes on day 1; or ramucirumab IV over 30-60 minutes and docetaxel IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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, 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]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

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]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., 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]

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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Pembrolizumab Shows Promise for NSCLC. [2015]

4. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]