Thread by @montypal

My take on #CheckMate274: Is adj CPI now SOC for #MIUC? Not yet. Here's the design presented today at @ASCO #GU21 - first, thanks to patients & investigators (#DrDeanBajorin, @MattGalsky) who should be commended for completing an adj trial in #bladdercancer - no small feat! (1/9)

First, a trip down memory lane. Here is the data from IMvigor010 - adj atezo v observation. No diff in DFS/OS, period. No difference based on PD-L1 status. Could it be PD-1 v PD-L1? Hard to prove. Could it be obs v pbo control? (2/9)

I stole this slide from @MattGalsky in a separate thread i came across. Here he nicely highlights the attrition on control and experimental arms. IMvigor010 lost a substantial proportion of folks due to "other" reasons on the observation arm. (3/9)

What did we learn today? We saw that #CheckMate274 met its primary endpoints of DFS in ITT & PD-L1+ populations. NO OS DATA, but as @MattGalsky reminded me, the analysis is event driven so couldn't be shown. "Tail on curve", which may drive OS, far more prounced in PD-L1+. (4/9)

If you do a deeper dive of non-urothelial tract RFS & distant MFS, benefit in ITT much more modest! Curves really coming together here. I would anticipate that these are the curves that are really going to drive OS. Some biological hypotheses coming next: (5/9)

This slide gives some key biological insights. Note that UTUC appears to not derive the same benefit here. Also (as the KM curves allude to) benefit really driven by PD-L1+. Is there a way to address pts who many NOT benefit from adj nivo? (6/9)

This is where #PROOF302 comes in. With infigratinib (a potent & specific FGFR3i), we plan to enroll FGFR3m pts (seen at higher rate in #UTUC) who (based on work from @FaltasLab) may have an immune-depleted phenotype. This #SUO-led study is enrolling now internationally. (7/9)

I also think we need a tie-breaker. This is where @apolo_andrea's @ALLIANCE_org #AMBASSADOR study comes in (great talks today at @ASCO #GU21 btw, #DrApolo!). Need to continue accruing. Mult adj studies have helped us resolve equipoise in #kidneycancer. Same story here. (8/9)

Bottom line: More clinical trials a must. And here's a teaser: We need to move data @tompowles1 presented at @myESMO #ESMOImmuno20 fwd. Out of all biomarkers I've seen so far, the @NateraOncology ctDNA work in #IMvigor010 is the best predictor of IO-assoc DFS & OS benefit. (9/9)