What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) involving monoclonal antibodies like Pembrolizumab and natural killer cell activators such as N-803 (ALT-803) can lead to several side effects. Pembrolizumab is associated with immune-related adverse events (irAEs) including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions, with severe effects in about 27% of patients. Natural killer cell activators may cause flu-like symptoms, fatigue, and injection site reactions. Combining these therapies could potentially increase the incidence and severity of these side effects, requiring careful patient monitoring.

What prior FDA approvals exist?

The FDA has approved several immunotherapy treatments for NSCLC that involve monoclonal antibodies targeting the PD-1/PD-L1 pathway. Pembrolizumab, a monoclonal antibody that inhibits PD-1, is approved for NSCLC with PD-L1 expression of at least 1% of tumor cells. Atezolizumab, another PD-L1 inhibitor, is approved for front-line treatment in patients with high PD-L1 expression (≥50% of tumor cells or ≥10% of tumor-infiltrating immune cells). Nivolumab, a PD-1 inhibitor, is also approved for previously treated advanced NSCLC. These treatments enhance the body's immune response against cancer cells, similar to the mechanism being studied in the N-803 (ALT-803) and Pembrolizumab trial.

What other types of research exist?

Promising alternatives for NSCLC treatment in 2024 include the combination of Emactuzumab and Atezolizumab, which has shown a manageable safety profile and considerable objective response rates, particularly in immune checkpoint blockade-experienced patients. Another option is the combination of Nivolumab and Ipilimumab, which has demonstrated efficacy in patients with advanced NSCLC, especially those with PD-L1 expression. These combinations offer potential benefits in terms of tumor response and progression-free survival.

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Immunostimulant

Combination Immunotherapy for Lung Cancer

Phase 2 & 3

Waitlist Available

Led By John M Wrangle

Research Sponsored by SWOG Cancer Research Network

Eligibility Criteria Checklist

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

Must have

Participants with spinal cord compression or brain metastases must have received local treatment to these metastases and remained clinically controlled and asymptomatic for at least 7 days following stereotactic radiation and/or 14 days following whole brain radiation, and prior to sub-study randomization

Participants with a known sensitizing mutation for which an FDA-approved targeted therapy for NSCLC exists (e.g. EGFR, ALK gene fusions, ROS1, BRAF, RET, NTRK, and MET sensitizing mutations), must have previously received at least one of the approved therapy(s)

Must not have

Participants must not have leptomeningeal disease that requires CNS-specific treatment prior to registration and must not be planning to receive the CNS-specific treatment through the first cycle of the protocol therapy

Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation in various organs, skin rashes, fatigue, potential blood disorders, and an increased risk of infections due to immune response alterations.

Eligibility Criteria

Inclusion Criteria

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

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

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I have a specific mutation in my lung cancer and have tried at least one approved treatment for it.

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My bilirubin levels are within the normal range, or up to 5 times the limit if I have liver metastases.

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I've had one treatment with anti-PD-1 or anti-PD-L1 for advanced cancer and my cancer got worse during or after treatment.

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I can safely receive standard cancer treatment options.

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My liver enzymes are within the required range for the study.

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

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My cancer can be seen on scans and has been checked recently.

Exclusion Criteria

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

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

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

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I have never needed steroids for lung inflammation not caused by an infection.

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I haven't had chemotherapy, immunotherapy, or experimental drugs in the last 3 weeks.

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I have not received treatments like ipilimumab or other immune therapies.

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I do not have another cancer that could affect this treatment's safety or results.

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I do not have severe liver problems or fluid buildup in my abdomen due to liver disease.

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I do not have severe heart disease or recent heart attacks.

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I haven't had a heart attack or stroke in the last 6 months.

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I have never had an organ transplant requiring immunosuppressants.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Overall survival

Secondary study objectives

Investigator-assessed progression-free survival (IA-PFS)

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm B (pembrolizumab, nogapendekin alfa)Experimental Treatment2 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 Control7 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3130

0 / 18Eligibility 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

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include immunotherapies such as monoclonal antibodies and agents that activate natural killer (NK) cells. Pembrolizumab, a monoclonal antibody, works by blocking the PD-1/PD-L1 pathway, which tumors use to evade the immune system, thereby allowing T-cells to attack cancer cells more effectively. N-803 (ALT-803) activates NK cells, enhancing their ability to target and destroy cancer cells. These mechanisms are crucial for NSCLC patients as they offer a way to harness the body's immune system to fight cancer, potentially leading to better outcomes and prolonged survival.