Tocagen just released data showing that in their phase 1 trial for injection of Toca511 into the resection cavity (NCT01470794), two of the partial responders became complete responders, bringing the total number of complete responses up to 6 out of 56 patients in the trial. However, in a subanalysis of the higher dose cohorts, 5 out of 23 were complete responders (22% complete response rate). These responses are also durable, with median duration of response being not yet reached at a median follow up of 35.7 months.
View press release here, and download the full PDF of the presentation here (Oct 27 2017 presentation).
Great news! And as written on Sciencedaily: "Dr. Chen also noted that five patients are experiencing a durable complete response with a median of at least 35.7 months. Within a subgroup of 23 patients, there were an additional five patients who achieved stable disease, bringing the number of patients who derived benefit from Toca 511 to 10 (or 43.4 percent of the patients who underwent Toca 511 therapy)."
ReplyDeleteOne question though: in this PDF presentation it mentions 6 CRs (4 IDHwt and 2 IDHmut). Last time we talked about this trial, it was said there were 4 IDHmut CRs. https://meetinglibrary.asco.org/record/152108/abstract
What am I missing?
The previous ASCO abstract mentions two IDHmut patients with complete response on Toca511/FC alone, one IDHmut patient with complete response on Toca511/FC + Bevacizumab, and one IDHmut patient with complete response after Toca511 injected intravenously. There is a separate clinical trial for intravenous injection of Toca511 so this last mentioned patient might have been in a different phase 1 trial.
DeleteThe discrepancy remains that the ASCO abstract speaks of three IDHmut patients and three IDH wt patients with response, and the more recent presentation speaks of two IDHmut and four IDHwt patients with response.
We must be missing something, and there is probably an explanation if we had access to all the data. Perhaps there was a mistaken diagnosis in one of the cases.
Just out of curiosity, where is this trial being conducted?
ReplyDeleteThe phase 1 trial, which is no longer recruiting, was recruiting in 5 states in the USA (California, Michigan, New Jersey, Ohio, Washington).
Deletehttps://clinicaltrials.gov/ct2/show/NCT01470794
The larger randomized phase 2/3 trial (Toca 5) has centers in the USA, Canada, Isreal and South Korea. The latest news is that this trial will be reopening as a phase 3 trial.
https://clinicaltrials.gov/ct2/show/study/NCT02414165?show_locs=Y#locn
There is also the phase 1 Toca 6 trial recruiting in Miami, Florida
https://clinicaltrials.gov/ct2/show/NCT02576665
Another trial in France uses similar gene therapy principles as the Tocagen trials. According to the latest post on this blog, this trial just recruited its first patient.
https://clinicaltrials.gov/ct2/show/NCT03294486
Thank you Stephen!
DeleteThis is encouraging news, even though the data are limited and interpreted.
ReplyDeleteWould be nice to know more about IDH and MGMT status of the full dataset. +2-3 years post 1st recurrence op for an AA or even GBM with IDH is - if not usual, then at least not rare.
Hope they admit a bulk of AA3 into the phase III trial given the *relatively* (only 4 patients) good results (actually 50% CR) for AA3´s in the high dose subset - wonder if the other two were IDH mutated or not.
A question: the results only reflects the trial of the "resection" cohort of 56 patients while the "intratumoural" and "intravenous" chorts trials were not part of this report, correct?
Looking forward to hearing more from these trials.
Preliminary results of this trial were published in June 2016 in Science Translational Medicine. Unfortunately there was no information on IDH1 status within the main study, and I don't have access to the supplementary material. If anyone has access to this journal it would be nice to have access to the Supplementary Materials for this study.
DeleteStudy abstract here:
http://stm.sciencemag.org/content/8/341/341ra75
The power point presentation published on the Tocagen website on Oct 27 (last week) includes toxicity data for all three trials, but the efficacy data is only for the resection trial (NCT01470794).
I don't think think there would be difference in efficacy in resection and intratumoral group, if resection is subtotal. And I guess this resections were subtotal, given the "complete response" observed.
DeleteBased on the above, Tocagen has been presenting new and updated data from several of their trials this weekend...
ReplyDeletehttp://ir.tocagen.com/phoenix.zhtml?c=254300&p=irol-newsArticle&ID=2315826
Especially the first trial priming Toca 511/FC treatment with T-cell therapy on paper sounds interesting (100% survival compared to ordinary 50% survival trweating with Toca 511/FC alone)
Anyone here have participated/have acces to materials or highlights from these presentations?
Most of those presentations haven't happened yet and are being shown this week. You can get more complete abstracts by going to https://sno.confex.com/sno/2017/meetingapp.cgi
ReplyDeleteBut you will only get abstracts, the detailed is only if you can log in.