FDA Grants Fast Track Designation to CAN-3110 for Recurrent High-Grade Glioma

Paul Peter Tak, MD, PhD, FMedSci

The FDA has granted fast track designation to CAN-3110, a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate, for use in adult patients with recurrent high-grade glioma.¹

The immunotherapy candidate agent was created to have both oncolytic and immune-boosting properties within the same treatment. Notably, the agent’s effectiveness is linked to the presence of nestin expression in cancerous cells. Data from a phase 1b trial (NCT03152318) with the use of the agent were published in Nature in October 2023 and showed that the use of CAN-3110 was well tolerated and associated with no dose-limiting toxicities among 41 evaluable patients.¹

In the trial, investigators reported a near doubling of median overall survival (OS) following a single injection of CAN-3110, resulting in an estimated OS of 11.6 months (95% CI, 7.8–14.9) vs a historical median OS of less than 6 to 9 months.^1,2 

Furthermore, positive HSV-1 serology served as a predictor of response, correlating with enhanced survival, with the median OS reaching 14.2 months (95% CI, 9.5-15.7) in this patient subgroup (n = 22). Additionally, enhanced infiltration of immune cells in the tumor microenvironment and expansion of the T-cell repertoire post-administration were linked to improved survival, suggesting that CAN-3110 may stimulate both local and systemic antitumoral responses.^1,2

“Receiving FDA fast track designation for CAN-3110 reinforces the critical need to find effective treatment options for patients with recurrent high-grade glioma and further supports the potential of CAN-3110 to address the challenges that the standard-of-care and conventional therapies have failed to meet,” Paul Peter Tak, MD, PhD, FMedSci, president and chief executive officer of Candel Therapeutics, stated in a news release.¹

High-grade gliomas exhibit aggressive features with poor survival outcomes, including rapid recurrence and limited response to traditional therapies.² Recurrent gliomas, such as recurrent glioblastomas, are associated with rapid neurological morbidity and survival below 10 months. Addressing this challenge, oncolytic viruses have emerged as a immunotherapeutic approach, leveraging virus-induced oncolysis to stimulate immune responses.²

Although several oncolytic viruses have shown potential in clinical trials, comprehensive immunological profiling in treated patients remains limited. Therefore, investigators of this phase 1b study aimed to elucidate data on the use of CAN-3110.²

“Recurrent high-grade glioma is one of the most aggressive malignancies for which there is no cure, representing a significant and urgent unmet need,” Antonio Chiocca, MD, PhD, head of the Department of Neurosurgery at Brigham and Women’s Hospital and a professor at Harvard Medical School in Boston, Massachusetts, stated in the news release.¹ “With fast track designation, I look forward to the potential of accelerating the development of CAN-3110 and the possibility of bringing this differentiated therapy to patients with recurrent high-grade glioma as we strive to improve outcomes and provide hope for patients and their families.”

The clinical trial divided patients with high-grade gliomas into 3 arms. Arm A (n = 41) included patients with recurrent disease who received a single intratumoral injection of CAN-3110 at a dose ranging from 1 x 10⁶ pfu to 1 x 10¹⁰ pfu, 9 of whom had multifocal/multicentric deep or bilateral tumors associated with poor survival.

Following observation of benefit with CAN-3110 in arm A, arm B (n = 9) was launched, in which patients received a single dose of cyclophosphamide at 24 mg/kg 2 days before CAN-3110 injection at doses of 1 x 10⁸ pfu (n=3) or 1 x 10⁹ pfu (n=6).

Finally, in arm C, 2 cohorts of 12 patients will receive a maximum of 6 injections of CAN-3110 over 4 months.

“As recently published in Nature, a strong local and systemic antitumoral response and improved survival in patients with recurrent high-grade glioma was observed following a single injection of CAN-3110,” Tak explained in the news release.

Serious adverse events, such as seizures requiring hospitalization and intervention, were observed in 2 patients; however, there were no dose-limiting toxicities or clinical/pathological evidence of ICP34.5-induced HSV-1 encephalitis or meningitis.² The data from the phase 1b trial therefore point to the relative human safety of CAN-3110 despite the presence of the HSV-1 ICP34.5 neurovirulence gene.

“We look forward to reporting additional data, including the potential benefits from multiple injections of CAN-3110, from the ongoing phase 1b clinical trial in the second half of 2024,” Tak concluded in the news release.¹

References

1. CAN-3110 receives FDA fast track designation for treatment of recurrent high-grade glioma. News Release. Candel Therapeutics. February 13, 2024. Accessed February 13, 2024. https://ir.candeltx.com/news-releases/news-release-details/can-3110-receives-fda-fast-track-designation-treatment-recurrent
2. Ling AL, Solomon IH, Landivar AM, et al. Clinical trial links oncolytic immunoactivation to survival in glioblastoma. Nature. 2023;623(7985):157-166. doi:10.1038/s41586-023-06623-2