Hi Pete!
The first U bolog trial will be a phase IB on leukemia - not phII. It will test K in combo with chemo agent cytarabine - so study will establish effective and safe combo dose, confirm biomarkers, safety and tolerability and possible efficacy, confirm proof of concept. U Bolog did say they wanted to do another combo study with an unnamed drug. (the 'major european pharma' drug). Perhaps they are setting the stage for a multiarm phII combo study specific to leukemias in late 2014 or 2015. The phIb should be ready to start any time now. It is common practice to run combined phIb and phII studies for combination therapies. I wouldn't be surprised to see them move from this Ib straight into a phII that includes both cytarabine and the second anonymous agent they said they want to test.
Then in-vitro studies at BI may be ongoing quietly, behind the scenes. Leo has said they were in combination with pfizer drugs for melanoma and renal cancers. So we may have some updates in store as we've only received one so far. Ctix has never clearly stated that BI has offered to do a human trial specific to these cancers. But ctix seems to be going for that and have completed the information sharing necessary for BI to receive a (SPORE) grant for a Kevetrin phII trial. No word on progress there- but if grant is application is completed this year and approved for 2014 - we will see this phII trial specifically targeted towards melanoma and renal cell cancers begin next year. I think that is likely - but probably not till q4 2014.
MDA has said they may carry the drug into phI trials dependent on what their preclinical data shows. They're studying multiple myeloma and lymphoma, some treatment resistant strains of those hematologic cancers, and they're also doing chemo-combo studies. Since the contract was only recently signed, I doubt they have started their preclinical investigation yet. And they only go further if they like the results they see in their own lab. They are bound by MTA contract to provide ctix with all of their research data. Ctix may decide they don't want to wait for an MDA phI and may themselves use the MDA data combined with the U Bolog data (and maybe even the BI data) to move into a multi-arm phII specifc to blood cancers. We'll see. This MDA investigation has nothing to do with ctix'x current phI trial - which is solid tumor trial. And yes - MDA could complete the preclinicals by end of year. They have the labpower to do that.
So right now Pete - we are looking at more preclinical research specific to blood cancers and another safety trial for a different blood cancer. No phase II's in sight yet - but they're coming. And it looks as though 2 or even 3 could be up and running at the same time.
As far as breakthru trials go - ctix will use the preclinical data from their own lab, U Bolog, BI, MDA - and decide from there. Looks like retinoblastoma now - but we may be surprised and see it become a treatment resistant hematologic cancer before the year is out. They are going to choose the most susceptible cancer that fits orphan/fast track/breakthru criteria. And they seem to be heavily focused on hematologic cancers of all types.
I can't answer your phII efficacy question without the phI data. Remember - this is completely novel agent. No comparison here. To say something like "usually efficacy in seen by third treatment cycle in phII" is meaningless - because we don't have a 'usually" to help us with comparison work. This is first in kind agent. We won't know until we know. Comparisons and historical trial data on other classes of drugs mean nothing here - though you'll see people make such meaningless comparisons all the time.
