Truseltiq (infigratinib)

Early termination limited the ability to draw definitive conclusions on the efficacy of infigratinib as first-line treatment of FGFR2-rearranged CCA. This study illustrates the challenges of powering confirmatory studies in biomarker-selected subpopulations of rare tumors and highlights the need for regulatory collaboration to develop pragmatic frameworks for assessing novel therapies in ultra-rare malignancies.

P3, N=114, Completed, QED Therapeutics, a BridgeBio company | Active, not recruiting --> Completed | Trial completion date: Apr 2026 --> Dec 2025

Importantly, pharmacological inhibition of FGFR1 using BGJ398 synergized with anti-PD-1 therapy, resulting in enhanced antitumor efficacy in preclinical models...Collectively, these findings identify FGFR1 as a key mediator of ICB resistance in HCC. Targeting FGFR1 represents a promising strategy to reprogram the immunosuppressive TME and enhance response to immunotherapy, with potential additional value as a predictive biomarker.

P1/2, N=11, Recruiting, Qed Therapeutics Inc.

P1, N=4, Terminated, Jennifer Lee Caswell-Jin | Phase classification: P1b --> P1

P=N/A, N=4, Completed, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2027 --> Feb 2026 | Trial primary completion date: Jan 2027 --> Feb 2026 | Active, not recruiting --> Completed

P2, N=135, Enrolling by invitation, QED Therapeutics, a BridgeBio company

P=N/A, N=4, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

Pharmacologically, dedicated inhibitors like Infigratinib have demonstrated anti-tumor activity in clinical Phase II trials for FGFR-altered recurrent gliomas, while the multi-kinase inhibitor Regorafenib has shown a modest survival benefit in recurrent GBM; however, mechanistic studies indicate that effective response often relies on co-targeting bypass pathways (e.g., CLK2) and mitigating the tumor's metabolic dependency. Crucially, limited drug exposure through the blood-brain barrier (BBB) continues to be the foremost challenge, dictating optimization efforts toward compounds with favorable pharmacokinetic properties and novel delivery platforms, such as the covalent inhibitor futibatinib and liposomal formulations, to enhance brain penetrance. In conclusion, the evolving molecular landscape validates FGFR alterations as a targetable niche in gliomas, and future success depends critically on integrating comprehensive next-generation sequencing to identify aggressive FGFR variants, developing next-generation inhibitors with superior BBB permeability, and implementing rational combination strategies to achieve durable clinical benefit.

Notably, combined inhibition of ALKBH5 (using ALKBH5-IN-5) and FGFR1 (using BGJ398/infigratinib) synergistically suppressed ZMIZ1-AS1-driven oncogenesis in vivo. Our study establishes the ALKBH5/ZMIZ1-AS1/PTBP1/FGFR1 signaling axis as a key driver of osteosarcoma progression and a promising target for therapeutic intervention.

P2, N=77, Recruiting, QED Therapeutics, a BridgeBio company | Not yet recruiting --> Recruiting

Advanced CCA remains largely inoperable, and combination gemcitabine plus cisplatin (GemCis) chemotherapy remains the standard treatment for patients affected by this disease...The FDA has approved the targeted therapies ivosidenib, pemigatinib, infigratinib, and futibatinib, as well as the immunotherapy durvalumab, for patients with CCA in recent years...While several promising advancements have been made, further research is required to improve outcomes for patients with CCA. This review provides an up-to-date, comprehensive overview of currently approved targeted therapies in CCA, as well as those under investigation.