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F - Immunological Aspects of Gene Therapy and Vaccines -> Immunological Aspects of Gene Therapy and Vaccines (Includes host responses, therapy/prevention of infectious diseases; excludes cancer immunotherapy and cancer vaccines)

Safety and Survival Outcomes in Recurrent High-Grade Glioma Patients Treated with CAN-3110, a First-in-Class ICP34.5 Expressing Oncolytic HSV1

Type: Oral Abstract Session

Presentation Details
Session Title: Late-Breaking Abstracts 1
Location: Room 515 AB
Start Time: 5/19/2023 8:45
End Time: 5/19/2023 9:00

Background: Recurrent high-grade glioma (rHGG) is a treatment-refractory cancer, characterized by a strongly immunosuppressive tumor microenvironment. Based on historical data, overall survival is < 6-9 months. CAN-3110 is a HSV-1 oncolytic viral immunotherapy engineered to express one copy of the ICP34.5 gene under the transcriptional control of the Nestin promoter. This modification largely restricts CAN-3110 replication and oncolytic activity to Nestin+ tumor cells. Here, we report the results of the first 50 rHGG patients treated with CAN-3110. Methods: The clinical trial comprised 2 arms. In arm A, 41 patients with rHGG were treated by a single intratumoral injection of CAN-3110 (dose ranging from 1x106 plaque forming units (pfu) to 1x1010 pfu), including 9 patients with multifocal/multicentric, bilateral tumors, characterized by poor survival. After showing tolerability of this regimen without dose-limiting toxicity, patients in arm B (n=9) were treated with a single high dose of cyclophosphamide (24 mg/kg), 2 days before CAN-3110 injection at doses of 1 x 108 pfu (n=3) and 1 x 109 pfu (n=6). Results: For arm A, median age was 56 years (range 27-74); 21 females, 20 males; median baseline KPS 90 (range 70-100). For arm B, median age was 54 years (41-70); 3 females, 6 males; median baseline KPS 90 (80-90). Overall survival for patients in arm A has been reported before (mOS 11.6, SITC 2022); CAN-3110 administration was generally well tolerated. For patients in arm B, we report that CAN-3110 with cyclophosphamide pre-treatment was also well tolerated without dose limiting toxicities. Median OS in arm B is ongoing at 12.0 months (data cutoff March 13, 2023), confirming encouraging clinical activity of CAN-3110. Transformative responses were observed in individual patients in both arms, including responses in injected and uninjected lesions in multifocal disease. One patient, with multifocal disease, recruited in arm A, experienced significant tumor regression of both an injected and an uninjected lesion with significant improvement in his functional status and ability to go back to work for almost a full year without additional treatment. A recurrence occurred in a third new site about a year after CAN-310 injection; next a diagnostic procedure was performed to assess the nature of the new lesion, which was complicated by a stroke. The subject entered hospice care. A second patient (arm A) presenting with aggressive disease progression after neurosurgery, showed no tumor growth for up to 2 yrs after CAN-3110 injection. The patient died following a car accident. In a third patient (arm B), we observed continued shrinkage of tumor volume 1 yr after CAN-3110 treatment. This patient is currently in follow up, more than one year after CAN-3110 without additional treatment. Analysis of post treatment samples demonstrated evidence of CAN-3110 spread and replication in uninjected contralateral tumor tissue with CD8+ T cell infiltration, which may help to explain the clinical responses in uninjected tumors. Additional extensive biomarker studies including histological, transcriptomic and single cell sequencing are ongoing. Conclusions: Data in the first 50 patients with rHGG who received a single intratumoral injection of CAN-3110, supports the notion that this approach is generally well tolerated and may provide clinical improvement and survival benefit. We are now pursuing a repeat dosing regimen of CAN-3110 (up to 6 injections over 4 months) in patients with rHGG.

Francesca Barone1, Alexander Ling2, Isaac H. Solomon2, Ana Montalvo Landivar2, Hiroshi Nakashima2, Andrea Manzanera1, Maria Lucia Silva Polanco1, Andres Santos2, Nafisa Masud2, Patrick Wen3, Keith Leigon1, David Reardon1, Sengupta Soma4, Garrett Nichols1, Paul Peter Tak1, E. A. Chiocca2

1Candel Therapeutics, Needham, MA,2Brigham and Women’s Hospital, Boston, MA,3Dana-Farber Cancer Institute, Boston, MA,4University of Cincinnati, Cincinnati, OH
 F. Barone: None.

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