ID #754 JACOB: Joint Administration of cDNA for TP53, checkpOint inhibition and Boost/Hypofractionated radiation. A phase 0/1 study in children with recurrent, progressive or refractory CNS malignancies.
Adriana Fonseca, Kathleen Pirollo, Russell Cruz, SangSoo Kim, Matthew Ladra, Julia Batarseh, Heather Schniepp, Deyana Underwood, Lindsay Kilburn, Roger Packer, Esther Chang, Eugene HwangAbstract
Background
Aberrant p53 functionremainsa hallmark of resistant malignancy with no current effective treatment strategy.JACOB is a prospective, phase 0/1 clinical trial to evaluate the safety and efficacy of SGT-53, a novel nanoparticle containingWT TP53 cDNA, in combination with hypofractionated radiation and anti-PD-1antibody in children with recurrent, progressive, or refractory CNS malignancies. We will provide a preliminary report on the first patients treated with this novel approach.
Methods
The primary objectives are to describe MTD/RP2D of SGT-53 in this combinatorial strategy, describe toxicities, and measure pharmacokinetics of SGT-53. Secondary and exploratory endpoints will assess preliminary efficacy,evaluate the p53 phenotype, and characterize the patient immunophenotype and biomarkers. Patients initially receive SGT-53 twice a week, nivolumab biweekly, and up to 5 fractions of XRT. A maintenance phase of SGT-53 and anti-PD-1 maybe continued for up to 12 months.
Results
Three patients have been enrolled in the study. Diagnoses include, recurrent BCOR ITD, recurrent SHH-Medulloblastoma and recurrent Pineoblastoma. All three patients have been treated at dose level 0 (2.1mgDNA/m2). One patient completed the Induction/DLT monitoring phase, and two others have started therapy. Related adverse events were relatively minimal: grade 2 infusion reaction with nivolumab, grade1 headache, grade 2 hypoalbuminemia, and grade 1 anemia. No DLTs were observed.
Conclusion
Our preliminary experience suggests tolerability of the combination at the current dose level. The trial remains ongoing and we anticipate continued enrollment at the next dose level. Disease response evaluations will provide information on the preliminary efficacy of the combination.