Truseltiq (infigratinib)

In this study, by incorporating diverse molecular glue handles and amino acid-based degrons into the solvent-exposed exit vectors of infigratinib, we synthesized a library of 30 candidate MGDs...Mechanistic investigations revealed that the covalent engagement of the gluing handle is a critical determinant for successful proteasomal degradation of FGFR2. This work provides a framework for the rational transformation of kinase inhibitors into covalent molecular glue degraders, underscoring the potential of FGFR degradation as a next-generation precision medicine strategy for FGFR2-driven malignancies.

Notably, among these derivatives, compound 1a emerged as a potent inhibitor of four distinct FGFR subtypes, demonstrating superior efficacy in suppressing the proliferation of Huh7 hepatocellular carcinoma cells compared to BGJ398, a clinically validated FGFR inhibitor...In Balb/c mice bearing Huh7 xenografts, 1a achieved a 90.5% tumor growth inhibition rate at a dose of 50 mg/kg, with no discernible signs of systemic toxicity. Collectively, these findings indicate that 1a holds great potential as a broad-spectrum FGFR inhibitor for cancer treatment, supporting its further development in clinical settings.

Treatment with the FGFR inhibitor BGJ398 reduced tumor growth and decreased stromal FGFR3-positive components, suggesting that stromal FGFR3 may represent a potential microenvironmental vulnerability in CRC with peritoneal dissemination. This autologous CRC-mesothelial system provides a physiologically relevant platform for dissecting tumor-stroma interactions in peritoneal metastasis and may advance stromal-targeted therapeutic strategies.

P1/2, N=22, Not yet recruiting, Qed Therapeutics Inc.

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