A5030762553- Sarcoma Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Chronic Myeloid Leukemia Treatments
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Lymphoma Diagnosis and Treatment
- Quinazolinone synthesis and applications
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Treatments and Mutations
- Vascular Malformations Diagnosis and Treatment
- Tumors and Oncological Cases
- Neuroblastoma Research and Treatments
- Neurofibromatosis and Schwannoma Cases
National Cancer Institute
2022-2023
Center for Cancer Research
2023
National Institutes of Health
2022
Abstract Background Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many our previously published phase 1/2 trials (SPRINT, NCT01362803). At the data cutoff (DCO) of prior publications, 65% participants were still receiving treatment. This report presents up to 5 years additional safety efficacy from these studies. Methods manuscript includes 2, stratum study which included clinically...
Abstract Purpose: Antibodies against insulin-like growth factor (IGF) type 1 receptor have shown meaningful but transient tumor responses in patients with rhabdomyosarcoma (RMS). The SRC family member YES has been to mediate IGF (IGF-1R) antibody acquired resistance, and cotargeting IGF-1R resulted sustained murine RMS models. We conducted a phase I trial of the anti–IGF-1R ganitumab combined dasatinib, multi-kinase inhibitor targeting YES, (NCT03041701). Patients Methods:...
<p>Serial samples demonstrate recurrent loci with copy number alterations for each patient.</p>
<p>Fusion-positive RMS enhancer sites; Universal DNAase-hypersensitivity YES1 and IGF1R region sets</p>
<div>Abstract<p>Purpose: Antibodies against IGF-1R have shown meaningful but transient tumor responses in patients with rhabdomyosarcoma (RMS). The SRC family member YES has been to mediate antibody acquired resistance, and cotargeting resulted sustained murine RMS models. We conducted a phase I trial of the anti-IGF-1R ganitumab combined dasatinib, multi-kinase inhibitor targeting YES, (NCT03041701). Patients Methods: relapsed/refractory alveolar or embryonal measurable disease...
<p>Supplemental Protocol Information. A: Study Eligibility; B: Dasatinib dosing nomogram; C: dose modifications</p>
<p>Progression-free survival for full cohort of patients (A) and by dose level (B).</p>
<p>Supplemental Protocol Information. A: Study Eligibility; B: Dasatinib dosing nomogram; C: dose modifications</p>
<p>Fusion-positive RMS enhancer sites; Universal DNAase-hypersensitivity YES1 and IGF1R region sets</p>
<p>Progression-free survival for full cohort of patients (A) and by dose level (B).</p>
<p>Serial samples demonstrate recurrent loci with copy number alterations for each patient.</p>
<div>Abstract<p>Purpose: Antibodies against IGF-1R have shown meaningful but transient tumor responses in patients with rhabdomyosarcoma (RMS). The SRC family member YES has been to mediate antibody acquired resistance, and cotargeting resulted sustained murine RMS models. We conducted a phase I trial of the anti-IGF-1R ganitumab combined dasatinib, multi-kinase inhibitor targeting YES, (NCT03041701). Patients Methods: relapsed/refractory alveolar or embryonal measurable disease...
11561 Background: Antibodies against the insulin-like growth factor type 1 receptor (IGF1-R) have shown transient objective partial responses (PR) in patients with RMS followed by rapid development of resistance. Preclinical data demonstrate that activation SRC family kinase YES acts as a bypass resistance mechanism to IGF-1R targeting. Co-targeting and results sustained murine models. We developed phase I/II trial anti-IGF-1R antibody ganitumab combined multi-kinase inhibitor dasatinib...
<p>Progression-free survival for full cohort of patients (A) and by dose level (B).</p>