Neoadjuvant Aliya™ PEF Soft Tissue Ablation With Systemic Therapy in Early-Stage Resectable NSCLC (VIGOR)

Neoadjuvant Soft Tissue Ablation Utilizing Aliya™ Pulsed Electric Fields With Systemic Therapy in Early-Stage Resectable Non-Small Cell Lung Cancer (NSCLC)

A prospective, single-arm, non-randomized, multi-center, open-label study following patients with resectable stage IIB to IIIA non-small cell lung cancer after Pulsed Electric Fields (PEF) ablation who may be candidates for standard of care neoadjuvant use of checkpoint inhibitor (nivolumab) treatment plus platinum doublet chemotherapy.

Study Overview

• Status: Terminated
• Conditions: NSCLC
• Intervention / Treatment: Device: Aliya Pulsed Electric Fields (PEF) ablation; Drug: Nivolumab plus Platinum Doublet Chemotherapy; Drug: Standard of care neoadjuvant therapy; Other: Surgical Resection

Detailed Description

This study is designed to evaluate the pathologic response of soft tissue ablated with Pulsed Electric Fields (PEF) in patients with resectable stage IIB to IIIA NSCLC who may be candidates for standard of care neoadjuvant use of checkpoint inhibitor (nivolumab) treatment plus platinum doublet chemotherapy. The study will enroll adult patients with suspected or confirmed 8th ed. Stage IIb-IIIA non-small cell lung cancer (NSCLC) who are surgical candidates and have not yet received treatment for NSCLC. PEF ablation may be performed in conjunction with the clinically appropriate approach to collect standard of care biopsy samples to confirm disease progression. PEF ablation will be delivered via percutaneous approach utilizing the Galvanize Aliya™ System and the percutaneous Aliya Ablation Device.

SOC neoadjuvant systemic treatment will be delivered following PEF ablation delivery according to EGFR and ALK mutation status, tumor histology, and surgical candidacy. Patients will undergo surgical resection per standard of care.

The study will consent up to 15 adult patients in order to accrue at least five (5) patients who have completed surgical resection after receiving neoadjuvant therapy with nivolumab plus chemotherapy following PEF ablation.

The remaining patients (up to 10) not eligible for neoadjuvant nivolumab plus chemotherapy will receive either SOC systemic therapy post-PEF ablation followed by resection or, if not eligible for systemic therapy, will receive definitive surgery without neoadjuvant therapy as per institutional SOC.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19122
      • Temple University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient is 18 years of age or older
2. Radiographic findings consistent with a lesion with high pre-procedure probability of malignancy as determined by the investigator to be NSCLC 8th Ed. stage IIB- IIIA cancer or biopsy-confirmed NSCLC 8th Ed. stage IIB-IIIA and lesion size ≤ 5 cm in greatest dimension
3. Lesion is targetable for biopsy and PEF delivery per investigator opinion
4. Patient deemed able to complete neoadjuvant therapy according to their EGFR/ALK mutation status and specific histology (if clinically appropriate) and per the manufacturer's systemic therapy labeling
5. Patient has been deemed a potential candidate for definitive lung tissue resection by a qualified study investigator
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
7. Patient is able to adhere to protocol requirements
8. Patient is able to tolerate general anesthesia
9. Patient is cleared to undergo paralytic anesthesia
10. Patient has provided informed consent

Exclusion Criteria:

1. Presence of advanced, inoperable, or metastatic disease
2. Radiographically suspicious findings for stage IIIA patients indicating a single mediastinal lymph node > 3 cm or multiple mediastinal lymph nodes and, therefore, potentially inoperable
3. Patient has recurrent NSCLC or has previously been treated for NSCLC
4. Patient has received chemotherapy or any other cancer therapy in 2 years prior to PEF ablation
5. Prior treatment with any drug that targets T cell co-regulatory pathways (such as checkpoint inhibitors) in 2 years prior to PEF ablation
6. Patient requires or is likely to require a pneumonectomy
7. Patient has received any vaccine against infectious diseases (e.g., influenza, COVID-19, varicella, etc.) within 30 days of PEF procedure Patient is unable or unwilling to complete all required screening and/or follow-up assessments
8. 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

Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Aliya PEF ablation; Pulsed electric field treatment using the Aliya System

Device: Aliya Pulsed Electric Fields (PEF) ablation; Patients will undergo PEF ablation; Drug: Nivolumab plus Platinum Doublet Chemotherapy; If EGFR/ALK mutation negative, patients will receive standard of care dosing of three cycles of nivolumab at a dose of 360 mg every three weeks along with a platinum-based chemotherapy doublet (cisplatin or carboplatin plus pemetrexed for adenocarcinoma, cisplatin or carboplatin plus docetaxel, paclitaxel, or gemcitabine for squamous NSCLC) post-PEF ablation followed by resection.; Other Names: Carboplatinum; Gemcitabine; Paclitaxel; Pemetrexed; Cipsplatin; Drug: Standard of care neoadjuvant therapy; Patients not eligible for neoadjuvant nivolumab plus chemotherapy will receive standard of care systemic therapy post-PEF ablation followed by resection.; Other Names: Carboplatinum; Gemcitabine; Paclitaxel; Vinorelbine; Pemetrexed; Cipsplatin; Other: Surgical Resection; Patients not eligible for systemic therapy will receive definitive surgery without neoadjuvant therapy as per institutional standard of care post-PEF ablation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic response	Pathologic response (percentage of residual viable tumor cells) of the resected lesion ablated with PEF and in resected lymph nodes in patients who received standard of care neoadjuvant nivolumab plus chemotherapy prior to resection.	Surgical resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of R0 resection	R0 - no cancer cells seen microscopically at the primary tumor site	Surgical resection

Collaborators and Investigators

• Sponsor: Galvanize Therapeutics, Inc.
• Investigators: Study Chair: William Krimsky, MD, Chief Medical Officer

Publications and helpful links

General Publications

• Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.
• Hellmann MD, Chaft JE, William WN Jr, Rusch V, Pisters KM, Kalhor N, Pataer A, Travis WD, Swisher SG, Kris MG; University of Texas MD Anderson Lung Cancer Collaborative Group. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint. Lancet Oncol. 2014 Jan;15(1):e42-50. doi: 10.1016/S1470-2045(13)70334-6.

Helpful Links

• CheckMate 816 Clinical Study

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Actual): February 8, 2024
• Study Completion (Actual): March 18, 2024

Study Registration Dates

• First Submitted: October 13, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 17, 2022

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; Nivolumab; Cisplatin; Immune Checkpoint Inhibitors; Lung Diseases; Pemetrexed; Antineoplastic Agents; Thoracic Neoplasms; Immunologic Factors; Lung Neoplasms; Docitaxel
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Nivolumab; Albumin-Bound Paclitaxel; Vinorelbine; Pemetrexed; Gemcitabine
• Other Study ID Numbers: CSP-00012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan of data sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No