FGFR3 Y373C

The MODAPLEX FGFR panel allows the stratification of bladder cancer patients by determination of the FGFR3 mutational and FGFR2/3 fusion status. The PCR-based FGFR assessment by MODAPLEX FGFR panel and therascreen FGFR kit is highly concordant (78/79). The MODAPLEX assays enable fast, local FGFR assessment in a multiplexed one-step approach within few hours.

We developed an effective AI system for detecting phenotypes associated with FGFR3 abnormalities that may be targetable by FGFR inhibitors. This system may allow cost and time savings in comparison to existing assays to screen bladder carcinomas for additional diagnostic testing.

Background: Interest in FGFR-targeted (FGFRi) therapies for UC or pan-tumor use is growing (ongoing clinical studies include erdafitinib (NCT05316155; NCT04172675; NCT03390504; NCT04083976), LOXO-435 (NCT05614739), and pemigatinib (NCT03914794) following accelerated approval of erdafitinib in locally advanced/metastatic (m) post-chemotherapy UC patients with FGFR2/3 (i.e., DNA mutations and fusions) alterations (ALT). FGFR-PRS (+) captured most ALT (+) tumors and an additional 2X more with similar FGFR pathway activation. FGFR-PRS (+) tumors were associated with gene enrichments for ontologies linked to FGFR3 signaling. The correlation of FGFR-PRS score with in vitro FGFRi activity provided initial utility of the signature, which is undergoing clinical evaluation in the ALAMANCE retrospective study of UC patients treated with FGFRi or other standard-of-care therapies.

Background: In view of the efficacy of FGFR targeting in early and advanced bladder cancer, as has been shown for erdafitinib in the THOR and NORSE trial, molecular testing of FGFR mutations and fusions will soon become clinical routine worldwide... PCR-based FGFR assessment by Therascreen and UroTyper is highly concordant and enables fast, local FGFR assessment within few hours. FGFR3 mutations are associated with increased TROP2 & NECTIN4 expression indicating potential synergistic options which warrants further exploration as part of molecularly stratified clinical trials.

The results showed a similar trend to previous studies, where FGFR GA was reported in approximately 20% of metastatic UC patients. No difference was found in the PFS and the estimated survival rate by FGFR2/3 GA-positive or -negative patients. Our data showed that treatment pressure did not alter the FGFR status commonly.

P2; Trial completion date: Aug 2023 --> Aug 2025 | Trial primary completion date: Aug 2023 --> Aug 2025

P1, N=169, Recruiting, Abbisko Therapeutics Co, Ltd | Not yet recruiting --> Recruiting | Initiation date: Dec 2022 --> Jun 2023

A positive somatic mutational status of the FGFR3 gene was statistically significantly more common in the group of papillary low-grade non-muscle-invasive BC, demonstrating basal p16 IHC staining. In the study sample, there was no statistically significant relationship between the FGFR3 status of BC and gender and age differences, TILs, MMR status, PD-L1 status (SP142 and 22C3), and p16 status. The results of the study indicate the need to determine the FGFR3 status in patients with BC for further prescription of personalized therapy.

P3; N=218 --> 39 | Trial completion date: Jan 2025 --> Jan 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2024 --> Jan 2023; The sponsor has decided to close the study due to the discontinuation of infigratinib development. The discontinuation of the study was not due to safety reasons.

This validation study supports the feasibility of applying NGS testing to leftover fixed urine cytology specimens. In addition, the potential utility of urine NGS testing as an adjunct to urine cytology in the early detection of HGUC for cases in which cytology is negative and/or atypical/suspicious should be investigated further.

P1, N=169, Not yet recruiting, Abbisko Therapeutics Co, Ltd