I sent few questions to the company shortly after Q2, company replied with some good answers that I thought I could share here because I believe they are very relevant:
Q1* ECRP, although you mentioned that this is a standard procedure do you also agree that it can be tricky and can add complexity to the treatment (feedback from doctors)?
fima Chem is a local treatment technology, involving a device which adds complexity compared to other administration routes. On the other hand, fima Chem ’s increased complexity has a good technological fit with bile duct cancer, since the light application is considered as an add-on to the routine ERCP procedures for this patient population.
Q2* Training the sites: since this a difficult to recruit indication, how can you make sure that the investigators are always kept updated with the procedure especially when it can take some time to recruit the next patient, will you be planning refresher courses for example and do you have the resources to have (a hands-on) follow up on 40 sites (may be more with Asia now)
Recruitment is a key risk factor for the RELEASE study’s success and therefore are measures, like site training, put in place to handle that risk.
Q3* As seen in the dose escalation study, not all patients survived 8 cycles of chemo, I believe 11 out 16 patients completed the treatment (68% hit rate). how will you be applying this learning in the pivotal phase study and how will this affect the timeline you set (for 60 events)
It is standard procedures that patients receive as many cycles of standard of care as possible. The RELEASE study is a randomized trial, meaning that maximum tolerable cycles will be applied in both the control- and the experimental study arms. The study statistics are based upon various elements to predict estimated time points for number of events and the communicated timelines are based on these predictions.
Q4* Delays with the treatment: due to photosensitivity as a side effect, a patient may not wish to undergo the procedure in certain seasons such as summer days due to light exposure whether this is for the 1st fimachem or 2nd fimachem treatment, hence a patient may ask to delay. will this affect the efficacy of the treatment considering the patient is already enrolled, do you consider these kinds of delays -if they happen- a handicap for the trial?
Photosensitivity is an additional side effect for the fima Chem treatment compared to standard of care. All side effects in general may reduce the recruitment rate, based on individual assessments of pros and cons by patients before they are enrolled to the study. PCI Biotech’s assessment, based on the safety outcome and experience from Phase I, is that fima Chem has a favourable safety profile seen in the context of the encouraging results.
Q5* Regarding IDMC safety review, I believe this will be reported for the first 8 patients. is there any requirements for a geographical spread or only first 8 patients will do (regardless of location). The reason I am asking is more related to genetic heterogeneity since the study will be going to Asia and if this could in a way affect the safety profile of the treatment.
The planned IDMC safety review after 8 patients undergoing two fima Chem treatments will be based on EU and US patients. We need to come back to how this is handled for Asia.
Q6* Regarding PPD, I have read that PPD has been challenging the “site first” approach for patients enrollment and started in summer 2018 rolling out a new enrollment model which is more patients-centric, I have put up a couple of links for you below to skim through (first article is written by a PPD executive director back in summer 2018). I would like to know if the pivotal study will be applying the new model, if not I would like to know the reason why since PPD claims/documented that the new model is time and cost effective for the sponsor, which also yields a better predictability.
The recruitment approach needs to be tailored to the demography and disease characteristics of the actual patient population. The “patient first“ model you are referring to is not applicable for bile duct cancer.
