It "lingered" with "L" to prove several hypotheses. One of which is no doubt the pattern of response in this treatment - It's trajectory. If we stopped measuring too soon we may not have captured the response trajectory of a delayed agent. It's like two airplanes with engine failure falling to the earth, only (DCVAX) finally gets 1 of it's engines started, albeit delayed and finally pulls up and levels off gliding back to earth, instead of crashing. Doing the hard work of waiting with DCVAX "L" in 1 indication could pay dividends for "L" and "Direct" in multiple indications including the current trials indication. We were already long in the tooth on this trial, pot committed so to speak, so going all in and waiting just a little longer was a good risk/reward decision. Waiting still sucks...
but waiting could:
1. Help clear up any muddiness with respect to PFS.
2. Elucidate the response trajectory difference that may not start immediately.
3. Improve the HR in this trial as the estimates will be based on different trajectories. And much of the information will be actual not estimate
4. Provide information on the Duration of Response.
5. Provide information on any manufacturing improvements, whether it was collection of APCs or improvement in the maturation(specific to the hour) as reflected by the Direct Patent or both. It certainly looks like the later patients are doing much better.
6. Provide biomarkers, imaging or some other tell tale sign that can be used to show a patient is responding and can help predict the duration of responses in the future.(You know like a replacement for PFS as a surrogate for actual long term survival)
6. This could speed up future trials in other indications for L and Direct and confirm trial design and manufacturing design.
Those 100's of other treatments being developed would also have to wait a long time to get the data we will have. Perhaps adjusting the manufacturing and maturation of the APCs will keep this "Cutting Edge". Are you positive that some changes in the "L" trial will not impact direct? They found a way to make APCs more aggressive in 2013/14/15, do you think they wouldn't want to apply that knowledge and test it in "L"? I don't believe "L" trial was specific with how long maturation should be, so if they made a minor tweak from 24 hours to 16-18 hours(method b) it would still follow protocol. The results could prove to NWBO that the maturation window for Method B is working and the hypothesis from the observation in Direct would be confirmed at least internally.
I simply disagree, this is as cutting edge as it gets. What other trials do you know of that have broad applicability, long duration of response, a fat tail of survivors ~35%+ at 36mo+, with zero toxicity or QOL issues? As a patient the risk reward for taking this drug appears only to be economical. ...and I think "L" was improved from the early stages of the trial(while still being under protocol). Improved by a slight nuance in either the purity of collection or the specific time of maturation. Like cooking a frozen pizza, 5 minutes is too short, 25 minutes is too long but 13 minutes is just right. I am sure LP wishes she knew in 2008 what she knows now. It would have probably changed the dilution picture in 2012-15. More of it would have occurred at a higher stock price earlier on. In any case the wait is nearly over.
Too bad BMS bought Celgene, maybe they have more $ in coffers for M&A because they certainly "get it" when it comes to immuno-oncology. https://www.immunooncologyhcp.bmsinformation.com/clinical-expectations/end-point-considerations