Combination Immunotherapy for Lung Cancer

Not currently recruiting at 357 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for advanced non-small cell lung cancer. It examines whether combining N-803, which might activate immune cells called natural killer cells, with pembrolizumab, an immunotherapy drug, can more effectively help the body fight lung cancer and prevent its spread. Participants whose lung cancer has continued to grow despite previous treatments might be suitable, especially if they have already tried immunotherapy with certain drugs. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in cancer therapy.

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.

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

Research suggests that N-803 (also known as ALT-803) could be a promising treatment for lung cancer. Studies show that N-803 might help the immune system by activating natural killer cells, which play a crucial role in fighting cancer. This treatment has generally been well-tolerated, but like any new drug, it can have side effects. However, the available sources do not fully report these side effects.

In contrast, pembrolizumab has more established evidence. Research has shown it to be effective and generally safe for treating non-small cell lung cancer. Over five years, patients have reported better survival rates compared to traditional chemotherapy. While usually well-tolerated, some patients have experienced side effects, as is common with many cancer treatments.

Both treatments aim to enhance the immune system's ability to target and fight cancer. If considering joining a trial, discussing potential side effects and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of N-803 (also known as nogapendekin alfa) and pembrolizumab for lung cancer because it offers a unique approach compared to traditional treatments. Unlike standard chemotherapy options such as docetaxel, gemcitabine, pemetrexed, and ramucirumab, this combination targets the immune system. N-803 is an engineered cytokine that boosts natural killer (NK) cells and T cells, enhancing the body's immune response to cancer cells. Pembrolizumab is an immune checkpoint inhibitor that helps prevent cancer cells from evading the immune system. Together, they aim to provide a more effective and potentially less toxic treatment by harnessing the body's natural defenses to fight cancer.

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

In this trial, one group of participants will receive a combination of N-803 (nogapendekin alfa) and pembrolizumab. Studies have shown this combination may be promising for treating advanced non-small cell lung cancer. N-803 activates natural killer cells, part of the immune system that can attack cancer cells. Pembrolizumab aids the immune system by blocking a pathway tumors use to hide. Some studies have found this combination effective in shrinking tumors and stabilizing the disease. Early research suggests these treatments together might prevent further cancer spread. Overall, this combination aims to enhance the body's natural defenses against cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

John M Wrangle

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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.

Your blood platelet count is at least 100,000 per microliter within the last 28 days before joining the study.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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]

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]

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 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 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 (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, 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2619

Lung-MAP S1800D: A phase II/III study of N-803 (ALT- ... Lung-MAP S1800D was a randomized study comparing N-803 plus pembrolizumab (NP) to investigators' choice standard-of-care chemotherapy (SoC) for previously ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05096663

Study Details | NCT05096663 | Testing the Use of ... Giving N-803 (ALT-803) and pembrolizumab may help shrink and stabilize lung cancer or prevent it from returning. Detailed Description. PRIMARY OBJECTIVES: I ...

3. immunitybio.com immunitybio.com/national-cancer-institute-selects-immunitybios-n-803-il-15-receptor-agonist-to-combine-with-keytruda-in-700-site-lung-map-clinical-trial-of-a-chemo-free-therapy/

National Cancer Institute Selects ImmunityBio's N-803 IL ... This Lung-MAP study will look at how N-803 could potentially bolster the effectiveness of Keytruda for patients with non-targetable cancer cell ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6089612/

ALT-803, an IL-15 superagonist, in combination with ... Characterization of outcomes in patients with metastatic non-small cell lung cancer treated with programmed cell death protein 1 inhibitors past RECIST ...

5. researchgate.net researchgate.net/publication/381456257_Lung-MAP_S1800D_A_phase_IIIII_study_of_N-803_ALT-803_plus_pembrolizumab_versus_standard_of_care_in_participants_with_stage_IV_or_recurrent_non-small_cell_lung_cancer_NSCLC_previously_treated_with_anti

Lung-MAP S1800D: A phase II/III study of N-803 (ALT- ... Methods: Lung-MAP S1800D was a randomized study comparing N-803 plus pembrolizumab (NP) to investigators' choice standard-of-care chemotherapy ( ...

6. pulmonologyadvisor.com pulmonologyadvisor.com/news/n-803-may-overcome-ici-resistance-in-nsclc/

N-803 May Overcome ICI Resistance in NSCLC N-803 to immune checkpoint inhibitor (ICI) therapy may overcome ICI resistance in patients with non-small cell lung cancer (NSCLC), according to research.

7. lungcancerstoday.com lungcancerstoday.com/post/phase-3-resq201a-nsclc-trial-to-evaluate-nogapendekin-alfa-inbakicept-plus-tislelizumab?uid=

Phase 3 ResQ201A-NSCLC Trial to Evaluate ... The IL-15 superagonist, also known as N-803, has previously demonstrated “the capability of rescuing T cells, and thus CPI efficacy,” through ...