Years ago we discovered that FGFR3 alterations are linked with a non-T cell-inflamed immune microenvironment in urothelial #BladderCancer #blcsm (1/6) cancerimmunolres.aacrjournals.org/content/early/… 
This finding was replicated in other data sets and suggested that FGFR3-active tumors may be less likely to respond to anti-PD1/L1 #Immunotherapy. It provided a strong rationale for combining FGFR inhibitors with anti-PD-L1 immunotherapy. (2/6)
This hypothesis was refined further by elegant data from @MattGalsky et al, which incorporated TGF-beta and EMT/stromal signatures, which further supported combining FGFR inhibitors and anti-PD-1/L1 (3/6) europeanurology.com/article/S0302-…
Excited to see this concept finally reach the clinic as @DrRosenbergMSK presents data at #ASCO20 from FORT-2, our phase 1b study of FGFR inhibition w/ rogaratinib + anti-PD-L1 tx w/ atezolizumab in 1L urothelial #BladderCancer ORR 44% w/ 16% CR (4/6)
meetinglibrary.asco.org/record/186057/…
meetinglibrary.asco.org/record/186057/…
Some final thoughts:
- Selecting patients by RNA expression works and is consistent w/ original finding that overexpression, w/ or w/out mutation leads to the same immunophenotype. ~50% of patients are FGFR1/3 positive by RNA scope
- 97% were PD-L1 negative as predicted (5/6)
- Selecting patients by RNA expression works and is consistent w/ original finding that overexpression, w/ or w/out mutation leads to the same immunophenotype. ~50% of patients are FGFR1/3 positive by RNA scope
- 97% were PD-L1 negative as predicted (5/6)
- All three patients who had PIK3CA mutations did not respond (important resistance pathway)
- Grade 3/4 TEAEs <20%
- The recommended phase II dose for rogaratinib in combination with atezolizumab is 600 mg.
- At that dose level the DCR was 87% & CR rate was 20%! (6/6)
- Grade 3/4 TEAEs <20%
- The recommended phase II dose for rogaratinib in combination with atezolizumab is 600 mg.
- At that dose level the DCR was 87% & CR rate was 20%! (6/6)
