CAN-3110 Earns FDA Fast Track Designation in Recurrent High-Grade Glioma

"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 HGG as we strive to improve outcomes and provide hope for patients and their families," according to Antonio Chiocca, MD, PhD.

The FDA has granted fast track designation to the herpes simplex virus-1 (HSV-1) viral immunotherapy agent CAN-3110 as a treatment to help improve overall survival (OS) for those with recurrent high-grade glioma (HGG), according to a press release from Candel Therapeutics.¹

“Recurrent HGG 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, said in the press release. “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 HGG as we strive to improve outcomes and provide hope for patients and their families.”

Investigators previously published findings from a phase 1b trial (NCT03152318) evaluating CAN-3110 for managing HGG in Nature.

Among 41 evaluable patients with recurrent HGG or glioblastoma, treatment with CAN-3110 yielded an estimated median OS of 11.6 months (95% CI, 7.8-14.9).² Additionally, the estimated median OS was 10.9 months (95% CI, 6.9-14.4) for 32 patients with IDH1/2 wild-type recurrent glioblastoma and 5.4 months (95% CI, 2.6-∞) for 4 patients with recurrent IDH-mutated anaplastic astrocytoma.

Investigators reported seizures leading to hospitalization and intervention in 2 patients; there were no dose-limiting toxicities or clinical evidence of ICP34.5-induced HSV1 encephalitis or meningitis. Overall, findings supported the safety of CAN-3110 across all dosing levels despite the presence of the HSV1 ICP34.5 gene.

“Receiving FDA fast track designation for CAN-3110 reinforces the critical need to find effective treatment options for patients with recurrent HGG 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 at Candel Therapeutics, said.¹ “As recently published in Nature, a strong local and systemic anti-tumoral response and improved survival in patients with recurrent HGG was observed following a single injection of CAN-3110. 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.”

In this open-label, single-center trial, investigators assessed treatment with CAN-3110 across multiple arms. In arm A, patients received CAN-3110 via intratumoral injection during biopsy surgery as part of a standard 3+3 dose escalation design with doses ranging from 1x10⁶ plaque forming units (pfu) to 1x10¹⁰ pfu. In arm B, patients received pretreatment cyclophosphamide at 24 mg/kg 2 days before CAN-3110 at 1x10⁸ pfu to 1x10⁹ pfu. Additionally, patients in arm C received up to 6 repeated doses of CAN-3110 at 108 pfus per time point followed by 10⁹ or 10⁷ pfus per time point.

The trial’s primary end point was the maximum tolerated dose. Secondary end points included MRI changes in permeability, volume, flow, viral shedding in saliva, and HSV1 antibody response.

Patients 18 years and older with an IDH wild-type glial tumor as confirmed via neuropathologist or a prior local pathology report were able to enroll on the trial. Additional eligibility criteria included having prior treatment with temozolomide plus concurrent external beam radiotherapy; adequate hematological, renal, and liver function; a Karnofsky performance status of 70 or higher; and an ability to undergo MRI screening with contrast.

Those with active or suspected autoimmune disorders, unacceptable anesthesia risk, or uncontrolled intercurrent illness were ineligible for enrollment on the trial. Patients were also unsuitable for enrollment if they had received prior treatment with an anti-VEGF or anti-VEGFR therapy.

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. http://tinyurl.com/mue4j9j2
2. Ling AL, Solomon IH, Landivar AM, et al. Clinical trial links oncolytic immunoactivation to survival in glioblastoma. Nature. 2023;623:157-166. doi:10.17605/OSF.IO/YBCG7).