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

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

1538 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination N-803 + Standard Care for Non-Small Cell Lung Cancer?

Research shows that combining pembrolizumab with carboplatin and nab-paclitaxel significantly improved survival rates in patients with advanced non-small cell lung cancer, suggesting that similar combinations could be effective. ^{1 2 3 4 5}

What safety data exists for N-803 + Standard Care for Non-Small Cell Lung Cancer?

Research shows that treatments involving nab-paclitaxel (a form of chemotherapy) combined with carboplatin have been studied for safety in non-small cell lung cancer. These studies generally focus on the safety and side effects of these drugs, which are important to consider when evaluating treatment options. ^{1 2 3 4 6}

What makes the drug combination of N-803, Carboplatin, Nab-paclitaxel, Pembrolizumab, and Pemetrexed unique for treating non-small cell lung cancer?

This drug combination is unique because it includes N-803, an IL-15 superagonist complex, which is designed to boost the immune system's response against cancer cells, alongside a mix of chemotherapy agents like Carboplatin, Nab-paclitaxel, and Pemetrexed, and the immunotherapy drug Pembrolizumab, which helps the immune system recognize and attack cancer cells. This multi-faceted approach aims to enhance treatment effectiveness by combining immune system activation with traditional chemotherapy. ^{1 2 3 4 7}

What is the purpose of this trial?

This trial tests N-803 with standard treatments for patients with severe lung cancer. N-803 aims to boost the immune system to fight cancer cells more effectively.

Research Team

Paula Bradshaw

Principal Investigator

Vice President, Clinical Business Operations

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Group II: Cohort C (Experimental) Experimental Treatment 1 Intervention

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

Group IV: Cohort A (Experimental) Experimental Treatment 1 Intervention

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 1 Intervention

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

Findings from Research

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]

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]

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 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 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]

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]

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]

References

1. United States 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. [2023]

2. United States 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. [2022]

3. England 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. [2023]

4. Thailand 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. [2022]

5. United States 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. [2020]

6. Greece pubmed.ncbi.nlm.nih.gov

Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). [2015]

7. United States 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. [2018]