William Krimsky, MD
Galvanize Therapeutics, Inc.
Disclosure(s): Galvanize Therapeutics: Management Position (Ongoing)
Aldeyturriaga J Flandes, MD
Director Bronchoscopy and Interventional Pulmonology Unit Section Head of Pulmonary Medicine
Jiménez Díaz Foundation
Erik van der Heijden H F M, MD
Associate Professor of Interventional Pulmonology
Radboud University Medical Centre
PEF induces a non-thermal tumor cell death, with potential to preserve the stromal architecture of sensitive structures, which may lead to an improved safety profile. This treat-and-resect study evaluates the safety and feasibility of delivering PEF to NSCLC.
Materials and Methods:
This study enrolled adults with suspected or confirmed NSCLC stage IA2-IB ( >1 to ≤4 cm tumor) scheduled for resection and with no tumor treatment in the previous 2 years. Both control and treatment groups were included, with 8 and 29 enrolled subjects, respectively. Treated subjects received PEF (investigational AliyaTM System GTI- 00018; Galvanize Therapeutics, CA) either percutaneously or endoscopically at time of biopsy prior to surgical resection. Blood, bronchoalveolar lavage (BAL) when applicable, and tissue samples were collected during the study for pre- and post-PEF comparison.
Safety and efficacy endpoints were evaluated, including assessment of PEF device- and/or procedure-related serious adverse events (SAE), changes in surgical approach, and histologic assessment of the PEF treatment zone and sensitive structures within, as determined by an independent pathologist.
PEF was successfully delivered in all treated subjects, including multiple lesions abutting and adjacent to the pleural surface and major fissures. No PEF-related AE or SAE were observed. Despite proximity to sensitive structures in some cases, PEF had no impact on the planned surgical resections.
PreliminaryassessmentsindicatePEFinducesacellulardepletionzone(CDZ)with an absence or near absence of tumor cellularity and a variable degree of fibroplasia and fibrosis without significantimpactonsensitivestructures.
From an initial cohort (n=9; 17-21 days post-PEF), 55 sensitive structures (including vessels, airways, and pleura) within the PEF-induced CDZs (some encroaching upon non-cancerous parenchyma) underwent histologic review. Intra-CDZ vessels, with sizes comparable to or smaller than arterioles, typically appeared intact, with a minority showing intimal fibrosis and/or chronic inflammation. Intra-CDZvesselsofsizeslargerthanarteriolesremainedintactandnormalpost-PEF. These observations were indistinguishable from those caused by typical tumor biology.
No PEF-related AEs were observed, and PEF delivery had no impact on planned surgical resections. Vessels larger than arterioles remained intact and normal within the PEF treatment zone. PEF delivery adjacent to sensitive structures appears to be feasible and without clinical or histopathological sequelae.