Gene therapy to Fight Glioblastoma Multiforme
Here we are at the fifteenth episode of Ben Williams’ guide translation project on treatment options for Glioblastoma Multiforme. This is chapter 11 of the guide. In this episode we talk about gene therapy and in particular the Toca511 / TocaFC treatment. The advice is still to use this information to discuss it with the medical team that is following you, where you can also indicate references to supporting scientific works.
The Glioblastoma.it for CUSP-ND for Emanuele fundraising campaign needs your help. In recent days I have been invited to the RADAR radio broadcast of the regional RAI of Friuli Venezia Giulia (Podcast of the Episode of March 9, 2021) and to the Trieste Live broadcast of Tele 4, a local television station (Video Recording of the Episode of March 16, 2021). Share the link in order to raise awareness as many people as possible. Enjoy the reading!
Toca 511 / TocaFC
Toca 511 is an engineered form of murine leukemia virus that supplies a specific gene to cancer cells, which then causes cancer cells to produce an enzyme called cytosine deaminase (CD). After the vector has spread throughout the tumor, patients receive a course of oral 5-FC, a prodrug of the common chemotherapy agent, 5-FU. The CD gene converts 5-FC to 5-FU, thus killing the cancer cell. The data from rodent models with this approach was impressive. The first human trials of the drug have begun the enrollment of patients in multiple treatment centers. Data from two ongoing Phase 1 clinical trials were published by the company (press release). Several partial responses have been observed, although the efficacy observed in rodent studies has not so far been found in human patients. A randomized phase II / III trial of this therapy for recurrent GBM or anaplastic astrocytoma began in late 2015 (NCT02414165).
In June 2016, the results of the Phase I study of Toca 511 / TocaFC for recurrent high-grade glioma patients undergoing surgery (NCT01470794), with Toca 511 injected directly into the resection cavity, were published in Science Translational Medicine. (344). A total of 43 patients, including 35 with glioblastoma, and the other eight with anaplastic astrocytoma underwent treatment. In the whole group of 43, there were 2 complete responses (both in patients with anaplastic astrocytoma), 2 partial responses (both in patients with glioblastoma), for a response rate of 9.3%. The disease stabilization rate was 18.6% and the clinical benefit rate (responses plus stabilizations) was 27.9%. It should be noted that this was a study aimed at evaluating the optimal dose and that many of the patients were probably treated at suboptimal doses of Toca 511. A clinical benefit rate of 36.7% was observed in the group. of high-dose Toca 511. 13 patients treated with lower doses of Toca 511 had a median survival of 11 months.
The study was open to patients with any number of previous relapses. Median survival for the 27 patients with glioblastoma at the first or second relapse was the same as in the whole group of 43 (including patients with anaplastic astrocytoma): 13.6 months. The results for the 27 patients with first or second relapse glioblastoma were compared with the results of a control group that received lomustine (CCNU) as part of a phase III study. Median survival from start of treatment for relapse was 7.1 months for the control group, and the longest survival (median 13.6 months) of patients in Toca 511 was statistically significant (HR = 0 , 45, p = 0.003). There were also fewer serious adverse events and an absence of haematological toxicity in the Toca 511 group compared to the control group of patients who received lomustine.
All phase I studies of Toca 511 / TocaFC for glioma are now closed and are no longer recruiting, a new phase II / III randomized study for high grade recurrent glioma is in the recruiting phase (NCT02414165), and one Phase I study for newly diagnosed high-grade glioma is not yet undergoing recruitment (NCT02598011).
(344) Cloughesy, Timothy F et al. “Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma.” Science translational medicine 8.341 (2016): 341ra75-341ra75.
I hope you enjoyed reading, I was as faithful as possible. Soon the next chapter! See you soon!