N-803 + Standard Care for Non-Small Cell Lung Cancer

Not currently recruiting at 30 trial locations

Overseen By Bruno Fang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ImmunityBio, Inc.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, Organ transplant, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with advanced non-small cell lung cancer (NSCLC). It evaluates the effectiveness and safety of these treatments alongside standard care. Participants may receive a mix of drugs, including N-803 (an IL-15 superagonist complex), carboplatin, nab-paclitaxel, pembrolizumab, and pemetrexed, to determine if they work better together. Individuals diagnosed with stage 3 or 4 NSCLC who have not received prior chemotherapy for advanced cancer might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot take medications that have an adverse reaction with the study drugs. 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 has shown that N-803, a drug still under investigation, has been studied for safety in people with non-small cell lung cancer. In earlier studies, N-803 was combined with other cancer treatments like pembrolizumab or nivolumab. These studies found that most patients tolerated the treatment well, with side effects usually mild or moderate. Some patients experienced more serious side effects, but these were less common.

N-803 is now in a phase 3 trial, where researchers confirm the treatment's effectiveness and gather more detailed safety information. Treatments in this phase have already shown promise in earlier studies, indicating they are generally safe. However, any treatment can have risks, and side effects can vary from person to person. It is important to discuss potential risks and benefits with a healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about N-803 for non-small cell lung cancer because it offers a fresh approach by enhancing the immune response against cancer cells. Unlike traditional treatments like chemotherapy, N-803 is an IL-15 superagonist that stimulates the activity of natural killer and T cells, boosting the body's natural defense mechanisms. This novel mechanism could lead to more effective and durable responses compared to existing therapies. Additionally, combining N-803 with standard care treatments like pembrolizumab and carboplatin might enhance overall treatment efficacy, offering new hope for patients battling this challenging condition.

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

Research has shown that N-803, one of the treatments in this trial, holds promise for treating non-small cell lung cancer. N-803 boosts the immune system's ability to fight cancer. In this trial, some participants will receive N-803 combined with pembrolizumab, a type of immunotherapy that has shown positive results in previous studies. Although N-803 is already approved for bladder cancer, it is now under study for lung cancer due to its potential to strengthen the body's defense against tumors. Early results are encouraging, suggesting that N-803 could complement standard cancer treatments effectively. ^{1 2 3 6 7}

Who Is on the Research Team?

Jayson Garmizo

Principal Investigator

Associate Director, Clinical Operations

Are You a Good Fit for This Trial?

This trial is for adults with stage 3 or 4 non-small cell lung cancer (NSCLC) who haven't had systemic chemotherapy for advanced/metastatic NSCLC. They must have tumors without certain genetic mutations, measurable tumor lesions, and an ECOG performance status of 0 or 1. Participants need to provide consent, tissue samples, agree to contraception use if applicable, and not be candidates for surgery or chemoradiation.

Inclusion Criteria

My tumor does not have specific genetic changes in EGFR, ALK, BRAF, ROS1, or NTRK.

Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines

The tumor can be measured and evaluated using a specific method called RECIST 1.1.

Exclusion Criteria

Known hypersensitivity to any component of the study medication(s)

I have a history of HIV or active hepatitis B or C.

I have or had inflammatory bowel disease like Crohn's or ulcerative colitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N-803 in combination with chemoimmunotherapy containing approved CPIs as first-line treatment for up to 2 years

Up to 104 weeks

Follow-up

Participants are monitored for disease progression, post-therapies, and survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• N-803
• Nab-paclitaxel
• Pembrolizumab
• Pemetrexed

Trial Overview The study compares the safety and effectiveness of N-803 combined with standard cancer treatments versus the standard treatments alone in NSCLC patients. It's a phase 3 trial where treatment continues up to two years unless there are issues like disease progression or unacceptable side effects.

How Is the Trial Designed?

Group I: Cohort D (Experimental) Experimental Treatment 1 Intervention

Group II: Cohort C (Experimental) Experimental Treatment 4 Interventions

Group III: Cohort B (Experimental) Experimental Treatment 1 Intervention

Group IV: Cohort A (Experimental) Experimental Treatment 2 Interventions

Group V: Cohort A (Control) Active Control 1 Intervention

Group VI: Cohort B (Control) Active Control 1 Intervention

Group VII: Cohort C (Control) Active Control 4 Interventions

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

ImmunityBio, Inc.

Lead Sponsor

Trials

75

Recruited

5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

In a study of 51 patients with malignant pleural mesothelioma, both pemetrexed with carboplatin (AC) and pemetrexed with cisplatin (AP) were found to be effective neoadjuvant chemotherapy regimens, with similar rates of disease control and surgical resection (81% for AC and 79% for AP).

However, the AP regimen was associated with a higher incidence of severe side effects, such as grade 3 anemia and increased fatigue, which could negatively affect patients' overall health and their ability to undergo surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). Pasello, G., Marulli, G., Polo, V., et al.[2015]

The combination of pemetrexed and nab-paclitaxel was found to be feasible and well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with a recommended phase II dose established at pemetrexed 500 mg/m² and nab-paclitaxel 260 mg/m².

In a phase II trial involving 37 patients, the treatment showed a response rate of 14% and a disease control rate of 46%, with a median overall survival of 8.8 months, indicating some efficacy in second and third-line therapy despite the early closure of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Ho, C., Davies, AM., Sangha, RS., et al.[2023]

A phase 3 study (J-AXEL) is underway to compare the efficacy and safety of nab-paclitaxel to docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC), involving randomization of patients to receive either treatment until disease progression or unacceptable toxicity.

The primary goal of the study is to demonstrate that nab-paclitaxel is noninferior to docetaxel in terms of overall survival, which could establish nab-paclitaxel as a new treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Rationale and Design for J-AXEL: A Randomized Phase 3 Study Comparing Nab-Paclitaxel With Docetaxel in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. Yoneshima, Y., Morita, S., Ando, M., et al.[2018]

Nab-paclitaxel significantly improves overall response (OR) and partial response (PR) rates in advanced non-small cell lung cancer (NSCLC), especially in squamous cell carcinoma and as a second-line treatment, based on a meta-analysis of 35 studies involving various trial designs.

While nab-paclitaxel shows marginal improvements in overall survival (OS) and progression-free survival (PFS), the evidence regarding its safety profile and reduction of adverse events remains inconclusive, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies. Suwannasom, N., Sriaksorn, N., Thepmalee, C., et al.[2023]

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

In the KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., et al.[2020]

Citations

1. 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 ...

2. 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 ...

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1556086422019104

An Interleukin-15 Superagonist Enables Antitumor Efficacy ... In vitro and in vivo data revealed differences in susceptibility of SCLC subtypes to lysis by NK cells and that NK cells activated by N-803 effectively lyse ...

5. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-025-01664-8

IL-15: from discovery to FDA approval In April 2024, the FDA approved the interleukin (IL)−15 superagonist, N-803 (Anktiva, nogapendekin alfa inbakicept-pmln), for the treatment of bladder cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02523469

Study Details | NCT02523469 | ALT-803 Plus Nivolumab in ... The purpose of the study is to define the safety and tolerability of this drug combination. The study will also define the response rate of patients with ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/24/17_Supplement/PR05/32237/Abstract-PR05-Safety-and-activity-of-the-IL-15-sIL

Safety and activity of the IL-15/sIL-15Rα complex ALT-803 in ... Safety and activity of the IL-15/sIL-15Rα complex ALT-803 in combination with the anti-PD1 mAb nivolumab in metastatic non-small cell lung ...