EPCT-02. PBTC-051: FIRST IN PEDIATRICS PHASE 1 STUDY OF CD40 AGONISTIC MONOCLONAL ANTIBODY APX005M IN PEDIATRIC SUBJECTS WITH RECURRENT/REFRACTORY BRAIN TUMORS
| Autor: | Alberto Broniscer, Tobey J. MacDonald, Ira J. Dunkel, Ovid Trifan, Holly Lindsay, Girish Dhall, Anna Vinitsky, Mehmet Kocak, Jason Fangusaro, Tina Young Poussaint, Arzu Onar-Thomas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty medicine.drug_class Central nervous system Neutropenia Monoclonal antibody Refractory Antigen Internal medicine Medicine AcademicSubjects/MED00300 Leukopenia biology business.industry CD40 Agonistic Monoclonal Antibody APX005M medicine.disease Early Phase Clinical Trials medicine.anatomical_structure biology.protein AcademicSubjects/MED00310 Neurology (clinical) Antibody medicine.symptom business |
| Zdroj: | Neuro-Oncology |
| ISSN: | 1523-5866 1522-8517 |
| Popis: | BACKGROUND CD40 is a co-stimulatory molecule expressed on antigen presenting cells (APCs). APX005M is a CD40 agonist monoclonal antibody which stimulates innate and adaptive anti-tumor immunity through activation of APCs, macrophages, and antigen-specific CD8+T-cells. Pediatric Brain Tumor Consortium study PBTC-051 is the first investigation of APX005M in pediatric patients and is evaluating the safety, recommended phase 2 dose (RP2D), pharmacokinetics, and preliminary efficacy of APX005M in children with central nervous system (CNS) tumors. RESULTS Accrual of patients with recurrent/refractory primary malignant CNS tumors (stratum 1) began in March 2018. 16 patients (2 ineligible) have enrolled on this stratum; 14 were treated. Dose escalation through 3 planned dose levels of APX005M was completed without excessive or unanticipated toxicities. The highest dose level (0.6 mg/kg q3 weeks) is the presumptive RP2D, and an expansion cohort is currently enrolling at this dose. 2 patients at dose level 3 have received >12 cycles of therapy. Grade 3 or higher adverse events at least possibly attributable to APX005M include 11 lymphopenia, 5 neutropenia, 5 leukopenia, 3 ALT elevations, 1 AST elevation, 1 thrombocytopenia, and 1 hypoalbuminemia. PK data will be available March 2020. Stratum 2 is now enrolling patients with post-radiation/pre-progression DIPG beginning at dose level 2, with 1 patient currently enrolled. CONCLUSION The CD40 agonistic antibody APX005M has demonstrated preliminary safety in pediatric patients with recurrent/refractory primary malignant CNS tumors and has a likely RP2D of 0.6 mg/kg q3 weeks in this population. Preliminary efficacy data are pending. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|