1. It sounds like none of the first 3 patients in Cohort 4 of SECURE have had a 3rd dose, even though this was supposed to happen in November.
I have found it confusing as well. A bit of digging and this is what I am getting.
Per the original protocol, the first 3 patients in Cohort 4 were meant to have 2 doses each - they did. A Safety Review then followed (4C, April 2024), and the SRC allowed progress to the recruitment of the second group of 3. This was related to just 2 doses, and proceeded as planned.
A change to the protocol!
4C, April 2024
- ... a change to the dosing schedule of cohort 4 from “2 doses” to “up to 4 doses” has been approved by the SRC and will be implemented following the required regulatory approvals. This will allow patients who are benefiting from 67Cu-SAR-bisPSMA to receive 2 additional doses under the SECuRE trial in cohort 4 (up to 4 doses in total).
4C, Jan 2025- The ongoing cohort 4 is the first to assess multiple doses of 67Cu-SAR-bisPSMA at the dose level of 12 GBq, with participants receiving a minimum of 2 and a maximum of 4 doses of 67Cu-SAR-bisPSMA at 12 GBq (4C, Jan 2025).
While the third dose was an option by November 2024, I too cant tell if anyone has received this. However, the decision to administer these additional doses (beyond the required two) was always optional: it depended on the patients need and also required regulatory approval, as well as SRC recommendations (this was received).In the Frazis interview, Alan does touch on this dosing scenario - adaptive dosing after 2 doses (From 38:35).
2. I can't make any sense of this statement regarding the second 3 patients in Cohort 4 "Recruitment of the additional three participantsinto cohort 4 of the dose escalation phase of the SECuRE trial is now complete, and the participants are currently in the safety and efficacy follow-up period with final participant completing final dose as planned." What does this mean? They've each had one dose? Two doses? Why is this being referred to the "final dose as planned"? Aren't they each supposed to have 4 doses?I did make some enquiries a while ago about recruitment and dosing, and they said we should treat those as very separate events. My understanding is that they sign them up, then do several things including pretreatment checks as well as imaging, before scheduling them for dosing. I think this makes sense since these are very sick patients, already on some treatments.
What I am still failing to get to is whether
'final dose as planned' refers to the old protocol (2nd dose), or the revised one that could be a 2nd, 3rd, or even a 4th dose. I'm sure someone here may be able to look at the timing and work this out (or at least, exclude the non feasible possibilities).
Either way, it means they have had at least 2 doses.Assuming the 2 doses were completed by everyone by end of December (more than 4 weeks ago), we may get an SRC review and results in days to a few weeks.
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April 2024 4C (pp 10)- Based on the favourable safety profile observed in the first 3 cohorts of the SECuRE trial, a change to the dosing schedule of cohort 4 from “2 doses” to “up to 4 doses” has been approved by the SRC and will be implemented following the required regulatory approvals. This will allow patients who are benefiting from 67Cu-SAR-bisPSMA to receive 2 additional doses under the SECuRE trial in cohort 4 (up to 4 doses in total).
- At the bottom of page 10, this is repeated on Study Design: *Patients in cohort 4 will receive 2 doses of 67Cu-SAR-bisPSMA (12GBq) according to the current study protocol. A protocol amendment is underway to allow 2 additional doses of 67Cu-SAR-bisPSMA in cohort 4. An SRC meeting will take place after participants receive their 2 doses, with a period of 6 weeks for safety follow-up.
November 2024 (MD's report, pp 8) Trial highlights to date- First 3 participants in Cohort 4had reductions in prostate-specific antigen (PSA) levels following 2 doses of 12GBq of 67Cu-SAR-bisPSMA, with the largest drop being 98% to date
- No DLTs have been observed to date
- Cohort 4 will be followed by a cohort expansion phase of the trial, pending safety evaluation
January 2025 4C (this report, pp 12)- In October 2024, the Safety Review Committee (SRC) completed the review of the safety data of the first 3 participants in cohort 4 of the SECuRE trial who received 2 doses of 12 GBq of 67Cu-SAR-bisPSMA.
- No dose limiting toxicities (DLTs) were reported in this cohort assessed
- The SRC recommended the study proceed as planned and enrol a further 3 participants to complete cohort 4.
- Recruitment into cohort 4 is now complete, and the additional 3 participants are currently in the safety and efficacy follow-up period assessing multiple administrations of 67Cu-SAR-bisPSMA.
(page 13)
- The ongoing cohort 4 is the first to assess multiple doses of 67Cu-SAR-bisPSMA at the dose level of 12 GBq, with participants receiving a minimum of 2 and a maximum of 4 doses of 67Cu-SAR-bisPSMA at 12 GBq.
- Cohort 4 is designed as a “3+3” cohort, where the first 3 participants received 2 therapy cycles followed by an SRC meeting before commencing recruitment of the final 3 participants, which is now complete. Following a 6-week period after these participants receive their 2 doses, another SRC will take place to assess safety and efficacy.
(20min delay)