Can a Phase 2 trial start before a Phase 1 trial wraps up? Why choose to do a Phase 1/2 trial instead of a separate Phase 1 trial followed by a separate Phase 2 trial? A few more observations about ongoing BET inhibitor Phase 1/2 or Phase 2 trials.....

The BET inhibitors (other than Resverlogix's RVX-208) that have been in clinical trials for the longest are Constellation's CPI-0610 (first dosing Sept 2013), Roche's R06870810 (formerly Tensha's TEN-010; first dosing Oct 2013), Merck's MK-8628 (formerly Oncoethix's OTX015; first dosing December 2012) and GlaxoSmithKline's GSK525762 (first dosing April 2012).

Of these four "oldies", only Constellation's CPI-0610 and GlaxoSmithKline's GSK525762 have Phase 2 trials listed. Constellation started their first Phase 1 trial with CPI-0610 back in September 2013 and this trial is still listed as ongoing and recruiting (though the entry hasn't been updated since November 2016). Despite their Phase 1 trial seemingly not completed, a Phase 2 trial was listed on ClinicalTrials.gov in December 2016 that is not yet recruiting. This appears to be a pure Phase 2 trial.

GSK has a couple of ongoing "Phase 2" trials for GSK525762, one of which was first listed Nov 2016 and started dosing in Feb 2017 and the other was first listed August 2017 and is not yet recruiting. However, the first GSK525762 Phase 1 trial that started dosing in April 2012 is still ongoing (last updated June 2017). If one looks carefully at the descriptions of the two "Phase 2" trials, it is clear that they are actually Phase 1/2 trials with a Phase 1 component that precedes the Phase 2 portion. Therefore, it is difficult to ascertain whether GSK525762 has truly progressed to Phase 2 status yet since they contain a preceding Phase 1 dose escalation/pharmacokinetic/pharmacodynamic portion.

Interesting that the other two "oldies" that were bought by Roche and Merck haven't progressed to Phase 2 yet. R06870810/TEN-010 is given subcutaneously, not orally, which may or may not be an issue. MK-8628/OTX015 had two Phase 1/2 trial registered while Oncoethix was still the owner, but one trial was withdrawn and one trial was terminated. Perhaps Roche and Merck want to do their own Phase 1 trials prior to comitting to Phase 2 and this may explain the lag in their molecules progressing to Phase 2 status. 

Many other companies have ongoing Phase 1/2 trials that, similar to the GSK525762 situation above, make it difficult to know if these are still in the Phase 1 stage or have progressed to the Phase 2 stage.  Amongst these other companies are Gilead (GS-5829), Incyte (INCB054329 and INCB057643) and BMS (BMS-986158). Note: I incorrectly referred to Incyte's trials as Phase 2 trials in my post yesterday.

Long story short.....it is difficult to compare the Zenith Phase 1 trials to these other BET inhibitor Phase 1/2 trials in terms of progress. 

BearDownAZ