- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Journal: Enhancing transcription-replication conflict targets ecDNA-positive cancers. (Pubmed Central) - Nov 7, 2024
In a gastric cancer model containing FGFR2 amplified on ecDNA, BBI-2779 suppresses tumour growth and prevents ecDNA-mediated acquired resistance to the pan-FGFR inhibitor infigratinib, resulting in potent and sustained tumour regression in mice. Transcription-replication conflict emerges as a target for ecDNA-directed therapy, exploiting a synthetic lethality of excess to treat cancer.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Trial completion date, Trial primary completion date, Metastases: Infigratinib for the Treatment of Advanced or Metastatic Solid Tumors in Patients With FGFR Gene Mutations (clinicaltrials.gov) - Oct 29, 2024
P2, N=17, Active, not recruiting,
Transcription-replication conflict emerges as a target for ecDNA-directed therapy, exploiting a synthetic lethality of excess to treat cancer. Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Preclinical, Journal: Achondroplasia: aligning mouse model with human clinical studies shows crucial importance of immediate postnatal start of the therapy. (Pubmed Central) - Oct 18, 2024
Animals were treated with the FGFR3 inhibitor infigratinib and the effect on skeleton was thoroughly examined...We provide clear evidence that immediate postnatal therapy is critical for normalization of skeletal growth in both the cranial base and long bones and the prevention of sequelae associated with achondroplasia. We also describe the limitations of early postnatal therapy, providing a paradigm-shifting argument for the development of prenatal therapy for achondroplasia.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma, Crysvita (burosumab-twza) / Ultragenyx, Kyowa Kirin
A Rare Case of Oncologic Osteomalacia () - Oct 12, 2024 - Abstract #KIDNEYWEEK2024KIDNEY_WEEK_5019;
In 2020, the FDA approved the use of Burosumab for hypophosphatemic hyperphosphaturic TIO in patients whose lesions are not amenable to excision. Novel therapies such as FGF Receptor tyrosine kinase inhibitor Infigratinib are underway..
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Monotherapy, Metastases: Evaluation of Infigratinib in Patients With Locally Advanced or Metastatic Gastric Cancer or GEJ Adenocarcinoma (clinicaltrials.gov) - Aug 14, 2024
P2, N=6, Terminated,
A novel therapeutic strategy of additional initial FGFR1 inhibition may be highly effective in suppressing the emergence of osimertinib- and ONO-7475-resistant cells. N=55 --> 6 | Trial completion date: Dec 2025 --> May 2024 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> May 2024; Business Reason
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma, navepegritide (TransCon CNP) / Ascendis, Voxzogo (vosoritide) / BioMarin
Review, Journal: Progress in managing children with achondroplasia. (Pubmed Central) - Aug 12, 2024
These include navepegritide, a long-acting form of C-type natriuretic peptide, and infigratinib, a tyrosine kinase receptor inhibitor, summarizing trial outcomes to date...These new treatment options highlight the importance of prompt prenatal identification and subsequent testing of a suspected fetus with achondroplasia and counseling of families. It is hoped that, in the near future, families will have the option to consider a range of effective targeted therapies that best suit their child with achondroplasia, starting from birth should they choose.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Enrollment closed, Trial primary completion date: Study of Infigratinib in Children with Achondroplasia (clinicaltrials.gov) - Jul 3, 2024
P2, N=84, Active, not recruiting,
Our findings provide novel insights into the metabolism of and potential DDIs implicating infigratinib. Recruiting --> Active, not recruiting | Trial primary completion date: May 2023 --> Oct 2024
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma, Xenical (orlistat) / Roche, GSK
Journal: Mitochondria targeted drug delivery system overcoming drug resistance in intrahepatic cholangiocarcinoma by reprogramming lipid metabolism. (Pubmed Central) - Jun 1, 2024
The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC...Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production...Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Journal: Dual blockage of PI3K-mTOR and FGFR induced autophagic cell death in cholangiocarcinoma cells. (Pubmed Central) - May 27, 2024
This study demonstrated that concurrent inhibition of the key FGFR/PI3K/mTOR pathways in CCA carcinogenesis enhances the suppression of CCA cells. The present findings indicate potential clinical implications for using combination treatment modalities in CCA therapy.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Enrollment status: Extension Study of Infigratinib in Children with Achondroplasia (ACH) (clinicaltrials.gov) - May 22, 2024
P2, N=280, Enrolling by invitation,
The present findings indicate potential clinical implications for using combination treatment modalities in CCA therapy. Recruiting --> Enrolling by invitation
- |||||||||| Developing behavioral intervention to support molecular testing of patients with biliary tract cancer. (Hall A; Poster Bd #: 510b) - Apr 24, 2024 - Abstract #ASCO2024ASCO_3723;
Genetic tumor testing identifies up to 40% of BTC patients with targetable mutations, leading to recent FDA approvals for FGFR2 inhibitors - pemigatinib, infigratinib, futibatinib, and IDH1 inhibitor ivosidenib...Ten participants are enrolled and have completed the first survey and intervention. This study is currently enrolling participants: GUIRB: STUDY00007119.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Trial completion, Trial completion date, Trial primary completion date, Surgery: Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer (clinicaltrials.gov) - Apr 19, 2024
P1/2, N=15, Completed,
This study is currently enrolling participants: GUIRB: STUDY00007119. Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Dec 2025 --> Apr 2024
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
P1 data, Journal: Phase 1b Trial Evaluating Tolerability and Activity of Targeted FGFR Inhibition in Localized Upper Tract Urothelial Carcinoma. (Pubmed Central) - Apr 4, 2024
P1/2
We initiated a biomarker-informed preoperative study of infigratinib, a Fibroblast Growth Factor Receptor (FGFR) inhibitor, in patients with localized upper tract urothelial carcinoma (UTUC), a population with high unmet needs and tumor with a high frequency of FGFR3 alterations...Renal preservation was enabled in a substantial proportion of participants. These data support the design of a biomarker-driven phase 2 trial of FGFR3 inhibition in this population with significant unmet clinical needs.
- |||||||||| Review, Journal: A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality. (Pubmed Central) - Apr 3, 2024
Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.
- |||||||||| Review, Journal: FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions. (Pubmed Central) - Mar 25, 2024
The next generation of small-molecule inhibitors, such as lirafugratinib and LOXO-435, and the FGFR2-specific antibody bemarituzumab are expected to have a reduced risk of hyperphosphataemia and the ability to overcome certain resistance mutations. In this Review, we describe the development and current clinical role of FGFR inhibitors and provide perspective on future research directions including expansion of the therapeutic indications for use of FGFR inhibitors, combination of these agents with immune-checkpoint inhibitors and the application of novel technologies, such as artificial intelligence.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma, linsitinib (ASP7487) / Sling Therap
The Synergistic Effect of Dual Targeting FGFR/FRS2 and IGF1R in Well-differentiated Liposarcoma and Dedifferentiated Liposarcoma (Exhibit Hall; Poster Board Number: 39) - Feb 18, 2024 - Abstract #USCAP2024USCAP_2409;
These findings indicated that the FGFR/FRS2 and IGF1R pathway could interact and commonly control the oncogenesis and biological behavior in WDL/DDL. Combining targeted therapy on activated FGFR/FRS2 and IGF1R may synergistically inhibit the formation and development of tumor, serving as a promising strategy for this tumor.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
The Activation of FGFR1/FRS2 Pathway and the Interaction with EGFR Pathway in Low-Grade Osteosarcoma (Exhibit Hall; Poster Board Number: 64) - Feb 18, 2024 - Abstract #USCAP2024USCAP_1949;
Our study showed FGFR1/FRS2 and EGFR pathways were involved and interacted in the tumorigenesis and progress of LGOS. The simultaneous inhibition of the FGFR1/FRS2 and EGFR pathways can produce effective and long-lasting tumor suppression, which suggest the potential therapeutic value of combined inhibition of these two pathways in LGOS treatment.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Trial completion date, Trial primary completion date: BGJ398 in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder (clinicaltrials.gov) - Feb 15, 2024
P=N/A, N=4, Active, not recruiting,
The simultaneous inhibition of the FGFR1/FRS2 and EGFR pathways can produce effective and long-lasting tumor suppression, which suggest the potential therapeutic value of combined inhibition of these two pathways in LGOS treatment. Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
- |||||||||| FDA event, Journal: An Expedition on Synthetic Methodology of FDA-approved Anticancer Drugs (2018-2021). (Pubmed Central) - Jan 30, 2024
The review comprises the key structural features, approval times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches of these approved drugs. These crucial details will benefit the scientific community for futuristic new developments in this arena.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Preclinical, Journal: Targeting FGFR3 signaling and drug repurposing for the treatment of SLC26A2-related chondrodysplasia in mouse model. (Pubmed Central) - Jan 29, 2024
Our results suggested that inhibition of FGFR3 signaling pathway overactivation and NVP-BGJ398 has promising therapeutic implications for the development of SLC26A2-related skeletal diseases in humans. Our data provide genetic and pharmacological evidence that targeting FGFR3 signaling via NVP-BGJ398 could be a route for the treatment of SLC26A2-associated skeletal disorders, which promisingly advances translational applications and therapeutic development.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Journal: Dual-hit strategy for therapeutic targeting of pancreatic cancer in patient-derived xenograft tumors. (Pubmed Central) - Jan 25, 2024
This dual-hit strategy of SMO and FGFR inhibition provides a clinically-translatable approach to compromise the profound impermeability of PDAC tumors. Furthermore, clinical deployment of DW-MR imaging could fulfill the essential clinical-translational requirement for patient stratification.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma, Pemazyre (pemigatinib) / Incyte, Specialised Therap
Targeting FGFR2 Splice Isoform In Preclinical Patient-Derived Organoids (PDOs) And PDXs- A New Opportunity For Personalised Care In Endometrial Cancer (Poster area) - Jan 18, 2024 - Abstract #ESGO2024ESGO_604;
All five models treated with cisplatin alone showed de novo resistance and no survival benefit. Seven-day treatment with BGJ398 revealed a significant reduction in angiogenesis and CD206?+?M2 macrophages.Conclusion These data collectively support the evaluation of FGFR inhibitors in a clinical trial either alone or in recombination with immune therapy and this opens a new opportunity for precision therapy in EC patients.
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Trial completion date, Trial primary completion date, Surgery: Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer (clinicaltrials.gov) - Dec 27, 2023
P1/2, N=15, Active, not recruiting,
Thus, development of combination strategies and next-generation FGFR inhibitors targeting the full spectrum of FGFR2 resistance mutations will be critical. Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
- |||||||||| Truseltiq (infigratinib) / BridgeBio, Pfizer, Xediton Pharma
Enrollment change, Trial withdrawal: Preoperative Nab-paclitaxel, Cisplatin, and Gemcitabine Chemotherapy With or Without Infigratinib Targeted Therapy for the Treatment of Resectable Intrahepatic Cholangiocarcinoma, The OPTIC Trial (clinicaltrials.gov) - Dec 26, 2023
P2, N=0, Withdrawn,
Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025 N=40 --> 0 | Not yet recruiting --> Withdrawn
|
