What side effects are associated with this type of intervention?

Common treatments for kidney cancer, particularly those involving immunotherapy such as IL-15 superagonists like N-803, often include immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors) and cytokine therapies (e.g., interleukin-2). Known side effects of these treatments can include flu-like symptoms (fever, chills, fatigue), gastrointestinal issues (nausea, diarrhea), skin reactions (rash, itching), and more severe immune-related adverse events such as colitis, pneumonitis, hepatitis, and endocrinopathies. These side effects result from the activation and proliferation of immune cells, which can sometimes attack healthy tissues.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of kidney cancer that focus on enhancing the immune response. Notable among these are immune checkpoint inhibitors such as nivolumab (Opdivo) and pembrolizumab (Keytruda), which target PD-1 to boost T cell activity. Additionally, combination therapies like nivolumab plus ipilimumab (Yervoy) have been approved for advanced renal cell carcinoma, leveraging the synergistic effects on T cells. While these treatments do not specifically include IL-15 superagonists like N-803, they share the common goal of enhancing the body's immune response to target cancer cells.

What other types of research exist?

Promising novel alternatives to N-803 for kidney cancer patients include: 1) Pembrolizumab plus Axitinib, which has shown improved outcomes in advanced renal cell carcinoma (KEYNOTE-426 trial). 2) Nivolumab plus Ipilimumab, which has demonstrated efficacy in first-line treatment of advanced renal cell carcinoma (CheckMate 214 trial). 3) Atezolizumab plus Bevacizumab, which has been effective in untreated metastatic renal cell carcinoma (IMmotion151 trial). 4) Cabozantinib in combination with Atezolizumab, which has shown positive results in advanced renal cell carcinoma (COSMIC-021 study).

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PD-1/PD-L1 Checkpoint Inhibitor

Combination Immunotherapy for Cancer

Phase 2

Recruiting

Research Sponsored by ImmunityBio, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Patients with genomic tumor aberrations should have received prior treatment with an FDA-approved targeted therapy (if available)

Must not have

Active systemic infection requiring parenteral antibiotic therapy

New York Heart Association (NYHA) Class III or IV heart failure, uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, or other clinical signs of severe cardiac dysfunction

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of treatments that aim to boost the immune system in patients whose cancer has progressed after previous treatments. Some patients may receive an additional therapy if their disease continues to progress.

Who is the study for?

This trial is for adults (18+) who've had prior treatment with PD-1/PD-L1 checkpoint inhibitors for various cancers, including lung, colorectal, and melanoma. They should have an ECOG performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must not be pregnant or nursing and agree to use effective contraception.

What is being tested?

The study tests combinations of immunotherapies: N-803 with different checkpoint inhibitors like Nivolumab and Avelumab, plus a cellular therapy called PD-L1 t-haNK for some patients. It's an open-label Phase IIb trial where treatments last up to two years with cycles every six weeks.

What are the potential side effects?

Potential side effects include reactions related to the immune system such as inflammation in organs, infusion-related reactions which can range from mild discomfort to more severe symptoms at the injection site, fatigue, possible increased risk of infections due to immune modulation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have had FDA-approved targeted therapy for my tumor's genetic changes.

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I received immunotherapy after my standard cancer treatment didn't work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently on IV antibiotics for an infection.

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I have severe heart issues, including heart failure or irregular heartbeats.

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I have not had heart failure, chest pain, or a heart attack in the last 6 months.

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I have had lung inflammation or immune-related lung issues.

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Treatment with PD-1/PD-L1 inhibitors is not safe for me.

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I am not pregnant or nursing.

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I am currently being treated for an autoimmune disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate

Secondary study objectives

Disease-specific Survival

Duration of Response

Incidence of Adverse Events

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Cohort 6Experimental Treatment2 Interventions

Patients who have progressed after an initial response (CR or PR) to a PD-1/PD-L1 checkpoint inhibitor but now exhibit acquired resistance. They have received exactly one line of anti-PD-1 or anti-PD-L1 therapy (either pembrolizumab or nivolumab) for advanced NSCLC (Stage IV or recurrent).

Group II: Cohort 5Experimental Treatment5 Interventions

Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4.

Group III: Cohort 4Experimental Treatment5 Interventions

Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.

Group IV: Cohort 3Experimental Treatment2 Interventions

Patients with NSCLC who had an initial CR or PR but subsequently relapsed on maintenance PD-1 checkpoint inhibitor therapy when they initially received checkpoint inhibitor therapy in combination with chemotherapy as first-line treatment.

Group V: Cohort 2Experimental Treatment2 Interventions

Patients with NSCLC whose tumors have high PD-L1 expression (TPS ≥ 50%) and who relapsed on a PD-1 checkpoint inhibitor after experiencing an initial CR or PR when they received checkpoint inhibitor as a single-agent for first-line treatment.

Group VI: Cohort 1Experimental Treatment5 Interventions

Patients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor. 1a - Non-small cell lung cancer 1b - Small cell lung cancer 1c - Urothelial carcinoma 1d - Head and neck squamous cell carcinoma 1e - Merkel cell carcinoma 1f - Melanoma 1g - Renal cell carcinoma 1h - Gastric cancer 1i - Cervical cancer 1j - Hepatocellular carcinoma 1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for kidney cancer include immunotherapies, targeted therapies, and checkpoint inhibitors. Immunotherapies like N-803, an IL-15 superagonist complex, enhance the proliferation and activation of natural killer (NK) cells and T cells, boosting the body's immune response against cancer cells. Checkpoint inhibitors, such as nivolumab and pembrolizumab, block proteins that prevent T cells from attacking cancer cells, thereby enhancing immune activity. Targeted therapies, like sunitinib and cabozantinib, inhibit specific proteins and pathways that promote cancer cell growth and survival. These treatments are crucial for kidney cancer patients as they offer more personalized and effective options, potentially improving outcomes and survival rates.

[Immunotherapy of metastatic renal cell cancer].