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Missed the talk? Here's a summary of latest data on the selective next-gen TRK inhibitor LOXO-195 (BAY 2731954). On-target resistance to current inhibitors driven by kinase mutations in 3 positions (SF, xDFG, GK) - SF likely most common. #AACR19 @sloan_kettering @AACR 1/x 
LOXO-195 evaluated in 2 programs: formal Phase 1 dose escalation and @FDAOncology #ExpandedAccess program 👏 (for pts unable to enroll in P1). Here's the key eligibility and combined patient demographics. 15 tumor types. 30 pts TRKi resistant, 1 intolerant. 2/x
Patients were enrolled regardless of specific TRKi resistance mechanism - so it was important to retrospectively define. This was done by: 1) local tissue sequencing and/or 2) central cfDNA - summary below. 3/x
Only observed DLTs (ataxia/dizziness) were on-target, consistent with CNS TRK inhibition. Drug very well tolerated in recommended dose range. Final dose and schedule selection ongoing. 4/x
Onto efficacy! TRK kinase mutant pts (n=20), confirmed ORR 45% (9/20). No responses in pts with bypass mutations (n=3). In remaining 6 pts, 1 complete response (in only pt enrolled based on intolerance to prior TRKi). 5/x
Here is duration of therapy for all pts. Responses were often durable. Of note, many pts were continued beyond RECIST progression due to ongoing clinical benefit - further extending the overall duration of benefit. We also saw this with larotrectinib. 6/x
Here are two individual patients whose experience illustrates how incorporation of LOXO-195 into the continuum of care may be valuable for TRK fusion-positive patients. I had the honor of personally treating both of these patients with @alexdrilon and @DavidHongMD 7/x
Here are our conclusions - I'll let these speak for themselves. This is real #TeamScience, too many investigators, institutions, companies & health agencies absolutely instrumental here to name individually. More to come! 8/fin
