Got an email back from Leo.
Let me preface by saying I have had a few questions on my mind for some time now, I am sure many of us have the same questions. I got very insightful responses, hopefully this sheds some light on a few trial relevant questions I know we all have wanted clarity on. Some very exciting stuff here, IMO.
Leo's answers in bold.
Hi Leo,
I have a few specific questions. If you could answer these purely at your leisure I would very much appreciate it.
So far, we have dosing as follows:
Cohort 0 - 10mg/m2
Cohort 1 - 20mg/m2
Cohort 2 - 30mg/m2
Cohort 3 - 60?
Cohort 4 - 120?
Cohort 5 - 240?
Cohort 6 - 480?
Cohort 7 - ??
1. If things go as well as possible from a safety standpoint, and there are no adverse effects in cohorts, will the dosing just continue to double as I speculate above? (doubling is what the protocol calls for assuming no AE or DLT, right?) It seems the animal data supports strong efficacy at higher doses . I am wondering at what cohort we could potentially get that high at DF.
We believe the dose for efficacy in humans to be about 100mg/m2 to 200mg/m2. It is important to note that in the next phases it could be determined if it is best to dose twice a week. We are now dosing 50 and could achieve 100 in the next cohort.
2. Why did cohort 2 only increase from 20 to 30? Although no DLT was reported, has there been an adverse effect in this cohort that caused the dosing to be increased only by half instead of a doubling? If so, was this AE non-related to Kevetrin and simply a by product of a very sick patient having other issues?
The dosing was increased 50% because there was redness on two patients at some point during the dosing. It was treated with Benadryl and went away. The safety review committee followed protocol and limited the dosing increase for the next cohort. It is important to note that the IRB now approved an amendment allowing for this type of redness not to effect dose limitations, and should this happen now, we would be able to go up 100%.
Also note these are stage 4 cancer patients who most often were treated elsewhere and have now come to this prestigious cancer center because there are no other options. My Mom had stage 4 and they needed to hydrate her and set up a saline IV. Just from that she went into a coma and died a few days later. Any dosing or even swallowing food or water can be a challenge for many of these patients.That is why the trial is set up in such a way to be extra cautious and protect the patient.
3. In your last PR, Dr. Menon stated as follows : "We are very pleased with the results to date especially considering the lower doses to date." Clever wording by the doctor . Can you clarify this statement? It seems to imply obviously that you are pleased with results beyond safety, otherwise why mention "considering the lower doses to date". Obviously, not sure what you can or cannot share here, but I along with several other shareholders found this choice of words very interesting. But us shareholders tend to over analyze things to death sometimes.
I cant discuss efficacy data. I can only point to the press release that we released at ASCO. Issues that we considered are number of cycles the patient has completed, nurses reports, and other information . When compared to other drug trials we are very pleased.
We are hopeful that very soon we will be at the efficacious dose.
Let me preface by saying I have had a few questions on my mind for some time now, I am sure many of us have the same questions. I got very insightful responses, hopefully this sheds some light on a few trial relevant questions I know we all have wanted clarity on. Some very exciting stuff here, IMO.
Leo's answers in bold.
Hi Leo,
I have a few specific questions. If you could answer these purely at your leisure I would very much appreciate it.
So far, we have dosing as follows:
Cohort 0 - 10mg/m2
Cohort 1 - 20mg/m2
Cohort 2 - 30mg/m2
Cohort 3 - 60?
Cohort 4 - 120?
Cohort 5 - 240?
Cohort 6 - 480?
Cohort 7 - ??
1. If things go as well as possible from a safety standpoint, and there are no adverse effects in cohorts, will the dosing just continue to double as I speculate above? (doubling is what the protocol calls for assuming no AE or DLT, right?) It seems the animal data supports strong efficacy at higher doses . I am wondering at what cohort we could potentially get that high at DF.
We believe the dose for efficacy in humans to be about 100mg/m2 to 200mg/m2. It is important to note that in the next phases it could be determined if it is best to dose twice a week. We are now dosing 50 and could achieve 100 in the next cohort.
2. Why did cohort 2 only increase from 20 to 30? Although no DLT was reported, has there been an adverse effect in this cohort that caused the dosing to be increased only by half instead of a doubling? If so, was this AE non-related to Kevetrin and simply a by product of a very sick patient having other issues?
The dosing was increased 50% because there was redness on two patients at some point during the dosing. It was treated with Benadryl and went away. The safety review committee followed protocol and limited the dosing increase for the next cohort. It is important to note that the IRB now approved an amendment allowing for this type of redness not to effect dose limitations, and should this happen now, we would be able to go up 100%.
Also note these are stage 4 cancer patients who most often were treated elsewhere and have now come to this prestigious cancer center because there are no other options. My Mom had stage 4 and they needed to hydrate her and set up a saline IV. Just from that she went into a coma and died a few days later. Any dosing or even swallowing food or water can be a challenge for many of these patients.That is why the trial is set up in such a way to be extra cautious and protect the patient.
3. In your last PR, Dr. Menon stated as follows : "We are very pleased with the results to date especially considering the lower doses to date." Clever wording by the doctor . Can you clarify this statement? It seems to imply obviously that you are pleased with results beyond safety, otherwise why mention "considering the lower doses to date". Obviously, not sure what you can or cannot share here, but I along with several other shareholders found this choice of words very interesting. But us shareholders tend to over analyze things to death sometimes.
I cant discuss efficacy data. I can only point to the press release that we released at ASCO. Issues that we considered are number of cycles the patient has completed, nurses reports, and other information . When compared to other drug trials we are very pleased.
We are hopeful that very soon we will be at the efficacious dose.
