One confusing thing regarding these numbers is that they don't seem to correspond to the initial trial design.
According to the trial design, the first stage of the Simon two stage decision point was after 9 patients had been enrolled and treated. If we include the original 6 patients treated in the dose escalation phase, that would mean the end of the first stage of the Simon two stage (and the decision point to proceed into the second stage) is reached at a total of 15 patients being enrolled. Assuming one patient responds in the first stage, a further 8 patients are recruited in the second stage of the Simon two stage design. This would mean a total of 23 patients enrolled and treated in the study to completion.
However, the Clinical programs update from Race said that 20 patients had been enrolled with a further two required to meet the first stage of the Simon two stage decision point, meaning that decision point would be hit at 22 patients recruited rather than 15 patients as per the initial design. This also can't be a mistake and mean the end of second stage of the two stage design because that is hit at 23 patients, not 22.
Also, as per the initial trial design it states that "If three or more of the patients treated in Stage 2 respond, the null hypothesis of treatment futility can be rejected". This would imply that the trial needs to progress into Stage 2, and the final 8 patients recruited, and that 3 of those 8 must respond, for the trial to be a success. The other possibility is that this is an error in the Race announcement and they mean instead that three or more of the patients in Phase 2 (Phase 1 being dose escalation) - not Stage 2 - must respond, i.e. 3 or more from the initial 9 in stage 1 and/or the 8 in stage 2 of Phase 2.
From the clinical programs update it sounds as though they are terminating the trial at the first stage decision point and not progressing into stage 2, so I hope it is indeed an error and they have at least 3 responses from Stage 1 of Phase 2 and this is enough to reject the null hypothesis.
This doesn't answer the question of why the patient numbers don't add up though. For example, if Stage 1 of Phase 2 was 9 patients total, that means they had recruited 7 patients at the clinical programs update time, and had 3 responses already (hence the decision to terminate the trial at the stage 1 decision point), which would mean a 43% response rate so far. However that would mean a total of 13 patients recruited at the update, not 20 as per the Race announcement.
Are you able to make better sense of these numbers
@johndprent? Are you able to clarify
@Davisite?
