What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include Tumor-Infiltrating Lymphocytes (TIL) therapy, immune checkpoint inhibitors (such as pembrolizumab and atezolizumab), and chemotherapy regimens (like carboplatin and paclitaxel). TIL therapy can cause side effects such as cytokine release syndrome, fever, chills, and fatigue. Immune checkpoint inhibitors may lead to immune-related adverse events including colitis, pneumonitis, hepatitis, endocrinopathies, and skin reactions. Chemotherapy often results in nausea, vomiting, hair loss, fatigue, and increased risk of infections due to bone marrow suppression. Early diagnosis and management of these side effects are crucial for patient care.

What prior FDA approvals exist?

The FDA has approved several immunotherapy and chemotherapy combinations for the treatment of Non-Small Cell Lung Cancer (NSCLC). Pembrolizumab, an anti-PD-1 therapy, has been approved in combination with chemotherapy for advanced squamous NSCLC, showing improved overall survival (OS) and progression-free survival (PFS) in the KEYNOTE-407 trial. Atezolizumab, another immunotherapy, has been approved in combination with bevacizumab and chemotherapy for nonsquamous NSCLC, demonstrating significant improvements in OS and PFS in the IMpower 150 trial. These approvals highlight the efficacy of combining immunotherapy with chemotherapy in treating advanced NSCLC.

What other types of research exist?

Promising novel alternatives to LN-145 for NSCLC patients include: 1) Osimertinib 160 mg for EGFR T790M-positive patients with brain metastases or leptomeningeal disease, showing efficacy in a phase II study. 2) Pembrolizumab-containing chemo-immunotherapy combinations, which are the current standard for naïve advanced NSCLC patients. 3) Nivolumab plus ipilimumab plus short-course chemotherapy, recently approved and noted for a reduced rate of severe adverse events. 4) Ramucirumab plus pembrolizumab, which has shown improved overall survival in patients with progressive disease after initial immunotherapy. 5) Cabozantinib, with or without atezolizumab, showing preliminary activity in advanced NSCLC previously treated with immunotherapy.

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CAR T-cell Therapy

Autologous LN-145 for Lung Cancer

Q: What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include chemotherapy, targeted therapy, immunotherapy, and Tumor-Infiltrating Lymphocytes (TIL) therapy like LN-145. Chemotherapy kills rapidly dividing cells, including cancer cells, but also affects normal cells. Targeted therapy uses drugs to specifically target genetic mutations or proteins that drive cancer growth, offering a more personalized treatment. Immunotherapy enhances the body's immune response against cancer cells by blocking proteins that suppress immune activity. TIL therapy involves extracting and expanding a patient's own immune cells that have infiltrated the tumor, then re-infusing them to attack the cancer. These treatments are crucial for NSCLC patients as they provide various options tailored to the specific characteristics of their cancer, potentially improving outcomes and quality of life.

Phase 2

Recruiting

Research Sponsored by Iovance Biotherapeutics, Inc.

Eligibility Criteria Checklist

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

Must have

Have historically or pathologically confirmed diagnosis of metastatic Stage IV NSCLC without EGFR, ALK, or ROS genomic alterations

ECOG performance status of 0 or 1

Must not have

Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or equivalent

Patients who have symptomatic, untreated brain metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests LN-145, a treatment using a patient's own lab-prepared immune cells, in patients with advanced lung cancer that has spread. The process includes reducing existing immune cells, infusing enhanced ones, and boosting their activity.

Who is the study for?

This trial is for adults with Stage IV non-small-cell lung cancer (NSCLC) without certain genetic mutations. Participants must have had disease progression after first-line therapy, be in good physical condition (ECOG status of 0 or 1), and have at least one tumor that can be surgically removed for treatment development. They should not have more than two prior lines of therapy and must agree to use effective birth control.

What is being tested?

The study is testing LN-145, a new potential treatment developed from the patient's own immune cells. It's an open-label phase 2 trial, meaning both researchers and participants know what treatment is being given, focusing on those with metastatic NSCLC who meet specific criteria.

What are the potential side effects?

While specific side effects are not listed here, treatments like LN-145 may cause immune-related reactions due to enhanced activity of the body’s own cells. This could potentially lead to inflammation in various organs, fatigue, fever-like symptoms, or allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

Select...

My lung cancer is stage IV and does not have EGFR, ALK, or ROS mutations.

Select...

I am fully active or can carry out light work.

Select...

My heart functions well and I have no symptoms of heart failure.

Select...

My lungs work well enough for normal activities.

Select...

I've had an approved targeted therapy for my cancer mutation, excluding EGFR, ALK, or ROS.

Select...

I have at least one tumor that can be surgically removed and another that can be measured.

Exclusion Criteria

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

Select...

I am taking 10 mg or more of prednisone daily or its equivalent.

Select...

I have brain metastases that have not been treated and are causing symptoms.

Select...

I have had another type of cancer in the last 3 years.

Select...

My cancer has EGFR, ALK, or ROS mutations.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 60 months for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Adverse Events

Complete Response Rate

Core Biopsies

+5 more

Side effects data

From 2022 Phase 2 trial • 64 Patients • NCT03083873

75%

Thrombocytopenia [4]

56%

Anaemia

56%

Hypophosphataemia

50%

Hypocalcaemia

44%

Diarrhoea

44%

Chills

44%

Pyrexia

44%

Hypomagnesaemia

44%

Hypotension

38%

Dyspnoea

31%

Leukopenia [1]

31%

Neutropenia [3]

31%

Febrile neutropenia

31%

Hypokalaemia

31%

Cough

25%

Constipation

25%

Dry mouth

25%

Hypoalbuminaemia

19%

Fatigue

19%

Pneumonia

19%

Infusion related reaction

19%

Decreased appetite

19%

Hypoglycaemia

19%

Hyponatraemia

19%

Confusional state

19%

Hypoxia

19%

Hypertension

13%

Oral pain

13%

Lymphopenia [2]

13%

Atrial fibrillation

13%

Sinus tachycardia

13%

Vomiting

13%

Oedema

13%

Capillary leak syndrome

13%

Respiratory failure

13%

Hypercalcaemia

13%

Hypernatraemia

13%

Arthralgia

13%

Back pain

13%

Acute kidney injury

13%

Pollakiuria

13%

Aspiration

13%

Pulmonary oedema

13%

Tachypnoea

13%

Petechiae

13%

Rash

13%

Embolism

Cytokine release syndrome

Mucosal infection

Muscle tightness

Hypersensitivity

Alopecia

Thrombocytosis

Supraventricular tachycardia

Tachycardia

Tachyarrhythmia

Visual impairment

Ventricular tachycardia

Cheilitis

Thrombocytopenia [2]

Dysphagia

Faeces discoloured

Nausea

Mouth haemorrhage

Mouth ulceration

Oral dysaesthesia

Face oedema

Localised oedema

Malaise

Multiple organ dysfunction syndrome

Swelling face

Oedema peripheral

Septic shock

Acute respiratory failure

Scrotal infection

Shock haemorrhagic

Sepsis

Soft tissue injury

Incision site pain

Tracheal haemorrhage

Wound haemorrhage

Alanine aminotransferase increased

Blood alkaline phosphatase increased

Blood bilirubin increased

Blood creatinine increased

Electrocardiogram QT prolonged

International normalised ratio increased

Weight decreased

Urine output decreased

Weight increased

Acidosis

Hyperkalaemia

Hypervolaemia

Hypermagnesaemia

Lactic acidosis

Malnutrition

Metabolic syndrome

Muscular weakness

Dizziness

Disturbance in attention

Headache

Dysgeusia

Encephalopathy

Peripheral sensory neuropathy

Neuropathy peripheral

Somnolence

Anxiety

Delirium

Insomnia

Irritability

Bladder pain

Dysuria

Oliguria

Haematuria

Micturition urgency

Haemoptysis

Dysphonia

Epistaxis

Laryngeal oedema

Pleural effusion

Respiratory distress

Rhinitis allergic

Rhinorrhoea

Decubitus ulcer

Purpura

Rash maculo-papular

Skin ulcer

Deep vein thrombosis

Distributive shock

Flushing

Haematoma

Pallor

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 3

Cohort 1

Cohort 2

Cohort 5

Cohort 4

Awards & Highlights

No Placebo-Only Group

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

Trial Design

5Treatment groups

Experimental Treatment

Group I: Retreatment CohortExperimental Treatment1 Intervention

Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4.

Group II: Cohort 4Experimental Treatment1 Intervention

Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients.

Group III: Cohort 3Experimental Treatment1 Intervention

Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation

Group IV: Cohort 2Experimental Treatment1 Intervention

Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment

Group V: Cohort 1Experimental Treatment1 Intervention

Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) \< 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

LN-145

2017

Completed Phase 2

~70

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

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include chemotherapy, targeted therapy, immunotherapy, and Tumor-Infiltrating Lymphocytes (TIL) therapy like LN-145. Chemotherapy kills rapidly dividing cells, including cancer cells, but also affects normal cells. Targeted therapy uses drugs to specifically target genetic mutations or proteins that drive cancer growth, offering a more personalized treatment. Immunotherapy enhances the body's immune response against cancer cells by blocking proteins that suppress immune activity. TIL therapy involves extracting and expanding a patient's own immune cells that have infiltrated the tumor, then re-infusing them to attack the cancer. These treatments are crucial for NSCLC patients as they provide various options tailored to the specific characteristics of their cancer, potentially improving outcomes and quality of life.