CTIM-09. ENRICHED TCR/BCR VDJ REARRANGEMENTS CORRELATE WITH MRI AND SURVIVAL OUTCOMES IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMA TREATED WITH CAN-3110

Autor: E Antonio Chiocca, Hiroshi Nakashima, Xiaokui Mo, Isaac Solomon, Alexander Ling, Jared Woods, Joshua Bernstock, Genaro Villa, Raziye Piranlioglu, Ana Montalvo Landivar, Nafisa Masud, Daniel Triggs, James Grant, Patrick Y Wen, Eudocia Lee, Lakshmi Nayak, Ugonma Chukwueke, Tracy Batchelor, David Krisky, Estuardo Aguilar-Cordova, Laura K Aguilar, Soledad Fernandez, Christopher Matheny, Andrea Manzanera, Francesca Barone, Paul Peter Tak, Keith Ligon, David A Reardon
Rok vydání: 2022
Předmět:
Zdroj: Neuro-Oncology. 24:vii61-vii61
ISSN: 1523-5866
1522-8517
Popis: BACKGROUND CAN-3110 (rQNestin34.5v2) is an HSV-1 oncolytic viral immunotherapy with one copy of the inflammatory ICP34.5 gene under transcriptional control of the Nestin glioma-specific promoter. We completed a phase 1 sequential dose-escalation trial of CAN-3110 in recurrent high-grade glioma (rHGG). METHODS CAN-3110 was injected intratumorally starting at 1x106 plaque forming units (pfu) and dose- escalated by half log up to 1x1010 pfu in biopsy confirmed rHGG. An expansion cohort of 12 patients was then accrued at 1x109 pfus. Blood and post-injection rHGG were collected. RESULTS 41 rHGG patients were treated (42 separate interventions): median age 56 years (range 27-74); 21 females, 20 males; median baseline KPS 90 (range 70-100). CAN-3110 administration was well-tolerated with no dose limiting toxicities. Median overall survival (mOS) was 11.9 months. Histologic and molecular analyses showed significantly increased T cell infiltration in post treatment samples with elevated T cell and/or B cell receptor (TCR/BCR) transcripts which correlated with patient survival (HR 0.26 for patients with elevated TCR/BCR rearrangements as compared to patients with low). Volumetric analyses of MRI suggest a trend between reduction in the relative change in tumor growth, TCR/BCRs enrichment and survival in CAN-3110 treated patients. CLINICAL IMPLICATIONS Administration of CAN-3110 into rHGG was well tolerated. OS of CAN-3110 treated subjects compare favorably to historical controls. The association of increased TCR/BCR transcripts with survival suggests that CAN-3110 induces T cell responses against rHGG, supporting further clinical development of CAN-3110 viral immunotherapy.
Databáze: OpenAIRE
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