A Clinical Evaluation of the Aliya™ System in Late Stage Cancer

Study Overview
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Brief Summary
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A prospective, single-arm, non-randomized, multi-center, open-label study following patients to 1 year. The study is designed to evaluate the safety and clinical utility of Pulsed Electric Field (PEF) treatment of advanced stage or metastatic cancer following progression on immunotherapy.

Detailed Description
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This study is designed to evaluate the safety and clinical utility of Pulsed Electric Field (PEF) treatment of advanced stage or metastatic cancer following progression on immunotherapy. The study will enroll adult patients with confirmed 8th ed. Stage IV non-small cell lung cancer (NSCLC), Stage IV renal cell carcinoma (RCC), or Stage IV hepatocellular carcinoma (HCC), who have experienced a response to checkpoint inhibitor (CPI) therapy (complete response (CR), partial response (PR), or stable disease (SD) as per RECIST 1.1) for a minimum of 6 months, and have documented radiologic progression (progressive disease (PD) as defined by RECIST 1.1) in up to five sites (non-central nervous system). PEF treatment delivery is to be performed in conjunction with the clinically appropriate approach to collect standard of care biopsy samples to confirm disease progression. The PI has the discretion to approach via endoluminal or percutaneous method if the target(s) is/are amenable. PEF treatment will be delivered to accessible new areas of growth on existing tumors or new tumors. Treatment may be delivered via either an endoluminal (bronchoscopic) or percutaneous approach at the discretion of the clinical investigator utilizing two available device configurations: Endoluminal: Galvanize Aliya System with compatible commercially available TBNA Needle and RF probe electrode Percutaneous: Galvanize Aliya System with compatible commercially available RF needle and RF probe electrode The study will enroll and treat up to 30 adult patients at up to 5 clinical sites.

Official Title
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INCITE LS: A Clinical Evaluation of the Aliya™ System in Late Stage Cancer

Conditions
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Cancer of Lung, Kidney or Liver

Intervention / Treatment
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* Device: Pulsed electric field treatment using the Aliya system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is eligible for inclusion if diagnosed and currently under physician care for one of the following advanced stage or metastatic conditions: Stage IV non-small cell lung cancer Stage IV hepatocellular carcinoma Stage IV renal cell carcinoma Patient is currently receiving PD-1/PD-L1 axis immunotherapy as their most recent line of therapy, either alone or in combination with standard of care systemic therapy for their malignancy. Patient has exhibited at least 6 months of response to PD-1/PD-L1 axis immunotherapy regimen (defined as complete response (CR), partial response (PR), or stable disease (SD) in their index tumors per RECIST 1.1) prior to progression. Patient has radiologically documented or confirmed progressive disease (per RECIST 1.1) defined as a total of ≤ 5 new areas of growth on existing tumors and/or new tumors. New tumors must be ≤ 2cm in longest diameter. New areas of growth on existing tumors must be ≤ 2cm in longest diameter. Tumors and new areas of growth must be deemed suitable by the investigator for complete treatment with PEF. Pathologic lymph nodes must be ≥ 15mm in shortest axis. In the judgement of the investigator, the patient is able to remain on PD-1/PD-L1 axis immunotherapy for at least 3 months after PEF treatment. New tumors and areas of growth on existing tumors are amenable to core or forceps biopsy in order to confirm disease progression. Patient must be willing to undergo tumor biopsy at PEF treatment delivery. Patient refuses surgery and/or stereotactic body radiotherapy (SBRT). Life expectancy ≥ 12 weeks. ECOG performance status 0-1 Exclusion Criteria: Patient has implanted lung devices or electronic devices. Patient is receiving bevacizumab concurrently with their PD-1/PD-L1 axis immunotherapy. Patient has received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) in another study within 21 days prior to study enrollment. Patient is scheduled to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for off-label cancer treatment while on this study. Patient has unresolved adverse reaction to immunotherapy that requires dose modification. Patient has received any radiation therapy within 6 weeks prior to study enrollment. Patient has leptomeningeal disease or active brain metastases that are not clinically controlled and asymptomatic for at least 14 days following treatment and prior to study enrollment or has residual neurological dysfunction and has not been off corticosteroids for at least seven days prior to study enrollment. Patient has an active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed Patient has received systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within seven days prior to study enrollment. Inhaled or topical steroids, and adrenal replacement doses ≤ 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease. Patient has any history of primary immunodeficiency. Patient has any history of organ transplant that requires use of immunosuppressives. Patient has clinical signs or symptoms of active tuberculosis infection. Patient has history of (non-infectious) pneumonitis that required steroids or current pneumonitis/interstitial lung disease. Patient has documented evidence of acute hepatitis or has an active or uncontrolled infection. Patient has undergone major surgery within 28 days prior to study enrollment or has planned for other major surgery to be performed while enrolled in the clinical trial. Patient is unable or unwilling to complete all required screening and/or follow-up assessments. Patient is currently enrolled in another interventional clinical trial or is receiving treatment with an investigational medication or medical device that conflicts with the study protocol. Patient for whom the investigator considers that the PEF treatment is not in the patient's best interest. Patient has active alcohol or drug addiction or any other condition that, in the investigator's opinion, would interfere with their ability to comply with the study requirements. Patient has any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single cohort consecutive case series
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliya PEF treatment<br> | Device: Pulsed electric field treatment using the Aliya system<br>* Patients will undergo pulsed electric field (PEF) treatment of up to 5 tumors (new or progressing) measuring ≤ 2cm in longest diameter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device and Procedure serious adverse event rate | The rate of system-related and procedure-related serious adverse events (SAEs) | 30 days | 
| Radiologic local control | Frequency with which local control of the tumor is attained using Pulsed Electric Field (PEF)-treated tumor(s) | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic response: lymphocytes | Changes from baseline in lymphocytes (CD3+, CD4+, CD8+, Treg, NK, Neutrophils; all analyzed as cells per mL) | all time points up to 1 year | 
| Immunologic response: cytokines | Changes from baseline in serum levels of cytokines (IL-2, IL-6, IL-10, IL-12; all analyzed as concentration in pg / mL) from blood samples | all time points up to 1 year | 
| Immunologic response: PD-L1 | Changes in PD-L1 percentage from biopsy samples | all time points up to 1 year |