A5031926846- Fibroblast Growth Factor Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Metastasis and carcinoma case studies
- Cancer Treatment and Pharmacology
- Monoclonal and Polyclonal Antibodies Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Neutropenia and Cancer Infections
- Platelet Disorders and Treatments
- Virus-based gene therapy research
- Pancreatic and Hepatic Oncology Research
- Hematopoietic Stem Cell Transplantation
- Pneumocystis jirovecii pneumonia detection and treatment
- Bone health and treatments
- Multiple Myeloma Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Radiopharmaceutical Chemistry and Applications
- Cancer Immunotherapy and Biomarkers
- Antifungal resistance and susceptibility
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Hypoxia, and Metabolism
- Chronic Lymphocytic Leukemia Research
- Bladder and Urothelial Cancer Treatments
- Hematological disorders and diagnostics
- Neuroendocrine Tumor Research Advances
C4 Therapeutics (United States)
2024
Novartis (United States)
2012-2020
Dana-Farber Cancer Institute
2017
Memorial Sloan Kettering Cancer Center
2017
The University of Texas MD Anderson Cancer Center
2017
Heidelberg University
2017
University Hospital Heidelberg
2017
Cornell University
2017
University Hospital Cologne
2017
Universidade Federal de São Paulo
2016
A trial of autologous T cells redirected to a specific mutation in glioblastoma patients illustrates mechanisms resistance.
BACKGROUND. CAR T cells are a promising therapy for hematologic malignancies. B cell maturation antigen (BCMA) is rational target in multiple myeloma (MM).
Purpose No standard treatment exists for patients with cholangiocarcinoma whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors FGFR alterations. Methods A multicenter, open-label, phase II study ClinicalTrials.gov identifier: NCT02150967)...
Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), recommended phase II (RP2D), and schedule, safety, pharmacokinetics, pharmacodynamics, antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients Methods Adult were treated escalating dosages BGJ398 5 150 mg once daily or 50 twice continuously...
Abstract BGJ398, a potent and selective pan-FGFR antagonist, was prospectively evaluated in patients with metastatic urothelial carcinoma bearing diverse array of FGFR3 alterations. Patients (N = 67) who were unable to receive platinum chemotherapy enrolled. The majority (70.1%) had received two or more prior antineoplastic therapies. BGJ398 administered orally at 125 mg/day on 3 weeks on, 1 week off schedule until unacceptable toxicity progression. primary endpoint the response rate. Among...
We determined the safety, pharmacokinetics, pharmacodynamics, and recommended phase II dose of MK-8776 (SCH 900776), a potent, selective checkpoint kinase 1 (Chk1) inhibitor, as monotherapy in combination with gemcitabine first-in-human I clinical trial patients advanced solid tumor malignancies.Forty-three were treated by intravenous infusion at seven levels ranging from 10 to 150 mg/m(2) then 800 (part A, n = 26) or 1,000 B, 17). Forty percent had three more prior treatment regimens, one...
Background. Oropharyngeal candidiasis is the most common opportunistic infection among persons infected with human immunodeficiency virus (HIV). Use of some agents hampered by lack efficacy, emergence resistance, adverse events, and need for intravenous administration. Posaconazole an extended-spectrum triazole potent in vitro activity against Candida species, including albicans, glabrata, krusei (including fluconazole-resistant strains).
We evaluated the efficacy and safety of oral posaconazole for human immunodeficiency virus (HIV)-infected subjects with oropharyngeal candidiasis (OPC) and/or esophageal (EC) who were clinically refractory to treatment fluconazole or itraconazole.Subjects confirmed OPC EC did not improve after receiving standard courses itraconazole eligible study enrollment. Subjects received either (400 mg twice daily) 3 days followed by once 25 (regimen A; 103 patients) 28 B; 96 patients). The primary end...
Summary Dickkopf‐1 ( DKK 1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease multiple myeloma. BHQ 880, human neutralizing IgG1 anti‐ 1 monoclonal antibody, is being investigated for its impact on myeloma‐related as an agent with potential anti‐myeloma activity. The primary objectives of this Phase IB study were to determine the maximum tolerated dose MTD ) 880 characterize dose‐limiting toxicity DLT escalating doses combination therapy...
Incorporation of cytarabine into DNA activates checkpoint kinase 1 (Chk1), which stabilizes stalled replication forks, induces S-phase slowing, and diminishes cytotoxicity. The selective Chk1 inhibitor SCH 900776 abrogates cytarabine-induced arrest enhances cytotoxicity in acute leukemia cell lines leukemic blasts vitro. To extend these findings to the clinical setting, we have conducted a phase I study 900776.Twenty-four adults with relapsed refractory leukemias received timed sequential,...
Multiple therapeutic agonists of death receptor 5 (DR5) have been developed and are under clinical evaluation. Although these demonstrate significant anti-tumor activity in preclinical models, the efficacy human cancer patients has notably disappointing. One possible explanation might be that current classes molecules not sufficiently potent to elicit response patients, particularly for dimeric antibody require secondary cross-linking via Fcγ receptors expressed on immune cells achieve...
Abstract Background: Fibroblast growth factor receptors (FGFRs) play a role in cell proliferation and survival. Genetic alterations of FGFRs can lead to deregulated activation various cancers, including squamous carcinoma (SCC) the lung urothelial bladder cancer. Here, we report on phase I study BGJ398 potent, selective pan-FGFR inhibitor. Methods: Eligible patients (pts; ≥ 18 years age) had tumors with any FGFR genetic alteration identified by central or local prescreening. Pts received...
335 Background: CCA is a hepatobiliary malignancy with poor prognosis and few treatment options following cytotoxic therapy in the first-line metastatic setting. The fibroblast growth factor receptor (FGFR) axis may promote tumorigenesis. FGFR2 fusions (in up to 17% of intrahepatic CCAs) predict FGFR inhibitor sensitivity. A prior phase 1 trial selective pan-FGFR BGJ398 showed antitumor activity pt harboring an fusion. Methods: This ongoing 2, open-label study evaluating oral 125 mg once...
Summary The effect of IL-6 on in vitro platelet function was investigated. Platelet-rich plasma (PRP) incubated with showed a dose dependent enhancement agonist induced maximum aggregation (AIMA) and secretion thromboxane B2 (TXB2) as measured by RIA, short term incubations. Dazoxiben (0.2 to 160 (µM) pretreated PRP aggregated ionophore A23187, inhibition TXB2 concomitant abrogation IL-6’s AIMA. A similar AIMA observed when these experiments were repeated using indomethacin. Further,...
To evaluate safety and efficacy of long-term posaconazole in HIV-infected patients with azole-refractory oropharyngeal candidiasis and/or esophageal candidiasis.In this noncomparative, open-label study, participants received oral 400 mg twice daily (bid) for 3 months. Enrolled (N = 100) included 60 from a previous 1-month acute study 40 posaconazole-naïve participants. Participants clinical response could be followed untreated up to 1 month afterwards. who relapsed during follow-up, showed...
8034 Background: Identifying molecular drivers in lung squamous cell carcinoma (SCC) is a major medical need since no targeted therapy available yet for this subtype. Fibroblast growth factor receptors (FGFRs) are physiologically involved proliferation and survival. Genetic alteration of FGFR genes leads to deregulated activation various cancers, FGFR1 amplification has been detected SCC. Here, we report on patients (pts) with FGFR1-amplified SCC treated phase 1 study BGJ398, potent,...
To evaluate the reliability of CD34/CD33 subset enumeration as a predictor hematopoietic repopulating potential in autologous blood stem-cell transplantation and to determine which patient treatment-related factors affect timing, quantity, type stem cells mobilized.We analyzed collections from 410 consecutive cancer patients who received mobilization therapy evaluated factors, including CD34+ quantities, that might influence engraftment kinetics transfusion requirements recipients.The...