Monday, June 22, 2015

ASCO 2015: MEDI0680 - a new anti-PD1!??

A little background:  There are two FDA approved anti-PD1 products on the market:  Nivolumab/Opdivo and Pembrolizumab/Keytruda (albeit only after you have failed ipi and, if BRAF positive, BRAFi as well!).  They have similar side effect profiles and equivalent response rates in melanoma, about 30-40%.  Response rates are probably much higher if your tumor is PD-L1 positive, but the jury is still out due to some conflicting data....probably the result of the (in)accuracy of the test(s) used in testing the tumor.  Cure Tech launched Pidilizumab/CT-011 , another anti-PD1 product, at about the same time that nivo went into trials, to dismal results - a 5.9% response rate - and I personally feel that was inflated.  Additionally, the poor ratties who joined that trial rather than the ones ongoing with nivo and, just a bit later, pembro, quickly realized it was not working...but were then banned from the other anti-PD1 trials because "they had already taken anti-PD1"!!!!!  They were not allowed effective anti-PD1 products until Merck and BMS opened their expanded access programs.  We have heard nothing more from CT-011...thank goodness.  Meanwhile AstraZeneca is working on MEDI-4736, an antiPD-L1 product, in non-small cell lung cancer.  They are combining it with Incyte's INCB24360 (an oral IDO inhibitor) in Phase 1/2 studies.  They are also utilizing MEDI-4736 with an investigational anti-CTLA4 monoclonal antibody tremelizmumab (the same category drug as ipi) as well as with dabrafenib and trametinib.  And finally, AstraZeneca is also evaluating MEDI-0680 (previously AMP-514) an anti-PD1 monoclonal antibody.  So.....

A phase 1, multicenter, open-label, first-in-human study to evaluate MEDI0680, an anti-programmed cell death-1 antibody, in patients with advanced malignancies.  Infante, Goel, Tavakkoli, et al.  J Clin Oncol 33, 2015.

PD-1 is an inhibitory regulator or checkpoint of T-cell activation.  MEDI0680 is a humanized immunoglobulin ...that blocks PD-L1 and PD-L2.  Blocking both PD-L1 and PD-L2 may provide more efficient pathway inhibition and may be more specific for different tumor groups in comparison to blocking either one alone.  This is an ongoing, phase 1, multicenter, open-label, first-in-human, dose-escalation study NCT02013804.  Recruitment is ongoing.

1. Blocking both the PD-L1 and PD-L2 pathways sounds cool and sure (????) to be effective.
2.  Hmmmm.....
3.  First-in-human....
4.  Recruitment is ongoing....sites include: NY, CT, Oregon.
5.  No prior BRAFi or immunotherapy (ipi, anti-PD1, or anti-PD-L1) allowed.
6.  Could be the next best thing.
7.  While I am certain combination therapies are what will win the war...I would make sure before signing on...that this treatment would not preclude my ability to take ipi or the current anti-PD1 products should I need them.

Ratties are the best.  Much love and best wishes. - c

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