ID #1122 Preliminary feasibility of an international, multidisciplinary central screening platform for the CONNECT TarGeT molecularly-guided phase 2 umbrella trial for children and young adults with newly-diagnosed high-grade glioma (HGG) including d
Margot Lazow, Kathleen Schieffer, Diana Thomas, Vera Paulson, Bonnie Cole, Christine Fuller, Santosh Valvi, Nick Gottardo, Michael Fisher, Ashley Plant, Ralph Salloum, Erin Crotty, Eugene Hwang, Anirban Das, Uri Tabori, Hamza Gorsi, Susan Chi, Sarah Leary, Patricia Baxter, Cynthia Hawkins, Michael Hubank, Thomas Jacques, David Jones, Felix Sahm, Mark Cowley, David Ziegler, Michael Rodriguez, Jason Dyke, Thomas Robertson, Joshua Palmer, Peter de Blank, Dong Anh, Khuong Quang, Kelsey Troyer, Brittany Konkle, Ryuma Tanaka, Rachid Drissi, Elaine Mardis, Darren Hargrave, Chris Jones, Maryam FouladiAbstract
Background
There is a critical need to develop novel, biologically-rational, and minimally toxic therapies for pediatric and young adult patients with HGG/DIPG, who have limited treatment options and a dismal prognosis. Motivated by genome-wide discoveries identifying recurrent, actionable somatic alterations within distinct molecular subgroups of pediatric HGG/DIPG, we developed TarGeT, an international, multi-institutional, multi-arm molecularly-guided phase 2 umbrella trial for children and young adults with newly-diagnosed HGG/DIPG.
Methods
The overarching screening protocol (TarGeT-SCR [NCT05839379]) aims to enroll >300 patients in total, for which comprehensive tumor molecular characterization (exome/genome sequencing, RNA-based fusion testing, methylation array) is performed at CONNECT regional genomics cores with rapid return of results. Alternatively, molecular testing performed outside the regional genomics core may be submitted for review. All cases undergo real-time central molecular, pathology, and clinical review by an international multidisciplinary screening team for eligibility confirmation and arm assignment based on presence of targetable genetic alterations. Treatment on TarGeT therapy arms is initiated by 35 days post radiation.
Results
As of 01/2026, TarGeT-SCR and initial TarGeT treatment arms have opened across US and Australian CONNECT sites, with further international expansion anticipated soon. Among the first 20 patients who have undergone screening, molecular profiling results have been returned within approximately 3 weeks (average: 20.5 days) from sample receipt for those submitting tissue. Average timeline of combined central molecular, pathology, and clinical arm assignment signoffs is < 1 week, facilitating enrollment of eligible patients onto assigned treatment arms within required time periods.
Conclusion
Results demonstrate preliminary feasibility of TarGeT-SCR in providing comprehensive molecular characterization of HGG/DIPG with rapid return of results and real-time central review for therapeutic arm assignment/ enrollment across a global consortium. This international multidisciplinary screening platform offers a precision medicine approach, expanding access to validated genomic profiling and targeted treatment for children and young adults with HGG/DIPG.