rogaratinib (BAY 1163877)

Using patient-derived organoids (PDOs), we demonstrated that FGFR-amplified PDOs respond to fulvestrant, palbociclib, and rogaratinib only when PIK3CA and ESR1 are wild-type. Toxicity was manageable and consistent with prior data. Our findings highlight biomarker-driven approaches as essential for refining FGFR-targeted strategies in this resistant population.

P2, N=48, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jul 2026 | Trial primary completion date: Jan 2025 --> Jul 2026

In our current practice we typically treat advanced symptomatic SDH-Def GIST with the anti-angiogenic TKIs, sequentially treating with sunitinib, regorafenib and pazopanib...Olverembatinib and rogaratinib have shown promising activity in pre-clinical models and small SDH-Def GIST cohorts. Other agents whose benefits are explored here include the immune checkpoint inhibitors (ICI) ipilimumab and nivolumab and temozolomide, whether as monotherapy or in combination with INBRX-109 (a pro-apoptotic antibody) or olaparib. Additional research into TKI agents with anti-vascular endothelial growth factor receptor (VEGFR) and anti-fibroblast growth factor receptor (FGFR) activity in this clinical setting is needed. Patients with SDH-Def will benefit more broadly from ongoing explorations of treatments with alternative mechanisms of action, especially those that exploit cellular pathways involved in SDH-Def GIST tumorigenesis.

Efficacy for this combination at the RP2D was observed in tumors with low PD-L1 and was not dependent on FGFR3 gene alterations, suggesting broad potential benefit for patients with locally advanced/metastatic UC and FGFR mRNA overexpression. ClinicalTrials.gov Identifier: NCT03473756.

P1, N=37, Completed, Bayer | Active, not recruiting --> Completed

P2, N=48, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1, N=37, Active, not recruiting, Bayer | Phase classification: P1b/2 --> P1

Triple FGFR1/2, CDK4/6 and ER blockade appears safe at standard drug dosages and shows promising clinical activity in second-line HR+ FGFR1/2+ BC patients progressing on CDK4/6i plus AI.

Ongoing trials are evaluating the use of erdafitinib in non-muscle invasive urothelial carcinoma as well as in combination with enfortumab vedotin in the metastatic setting, while other FGFR targeted agents such as infigratinib, AZD4547, rogaratinib and pemigatinib continue to be in development. Future challenges will include strategies to overcome FGFR acquired resistance and efficacy and safety of combination therapies with erdafitinib and other FGFR targeted agents.

P2, N=48, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

Six pts (16.21%) received targeted therapy (Erdafitinib/Rogaratinib) with no improved mOS compared to standard therapy (p = 0.026). Activating FGFR fusions in NSCLC are rare events. The majority of patients are elder males with smoking history and predominantly squamous histology. The most frequent co-mutation is TP53 with prolonged OS comparing to TP53 WT patients.

P1; Active, not recruiting --> Completed | N=19 --> 9