PNOC015: An Open Label Single Arm Study of MTX110 Delivered by Convection-enhanced Delivery (CED) in Patients with Diffuse Intrinsic Pontine Glioma (DIPG) Previously Treated with External Beam Radiation Therapy

Sabine Mueller, Cassie Kline, Javier Villanueva-Meyer, Carly Hoffman, Shannon Raber, Erin Bonner, Javad Nazarian, Shannon Lundy, Annette Molinaro, Michael Prados, Mariella Filbin, Nalin Gupta


Research support from:
Bristol Meyers Squibb
Del Mar

Rationale for Trial Design

  • Children with diffuse intrinsic pontine glioma (DIPG) conintue have a dismal prognosis with median survival rates of about 9 months
  • No standard therapy besides radiation therapy has been established
  • Potentially effective therapeutic agents may fail due to poor blood-brain barrier penetration
  • Direct intraparenchymal drug delivery such as CED can overcome these barriers and ensure adequate drug exposure to tumor cells
  • Panobinostat has been shown to be an effective cytotoxic agent across different DIPG model systems
  • MTX110, a soluble form of panobinostat, has favorable convection properties in prior large animal (pig) studies

PNOC 015 Trial Design

Newly diagnosed patient with DIPG after completion of standard of care radiation


Enrollment on PNOC015


Assignment to appropriate dose level with potential to dose escalated based on tolerability


Repeat CED with co-infusion of Prohance every 4 to 6 weeks pending tolerability and feasibility of ongoing disease control


7 eligible participants were enrolled between May 2018 – March 2020

  • Median age: 8 years (range 5-20)
  • Median number of CED cycles: 4 (range 2-8)
  • Median follow-up time from study enrollment: 418 days (range 137-614)
Sex Age at diagnosisPathology at diagnosisTotal treatment cycles (CED)Progression free survival (months)Overall survival (months)
F5Diffuse midline glioma H3K27M-mutant2414
M9Diffuse midline glioma H3K27M-mutant4717
M7Diffuse midline glioma H3K27M-mutant81426
M11NA – no biopsy done4821
M20Diffuse midline glioma H3K27M-mutant2921
M5Diffuse midline glioma H3K27M-mutant2311
M8Diffuse midline glioma H3K27M-mutant4511

PNOC 015 Adverse Events

  • Predominantly grade 1 toxicities
  • Five (5) grade 3 events
  • No grade 4 events
figure 2

CED of MTX110 leads to effective convection in DIPGs

PNOC015: Overall survival outcome

figure 4

PNOC015 Summary

  • CED with MTX-110 in patients with DIPG is feasible, tolerable, and may lead to prolonged survival
  • Co-infusion with Prohance can be used to determine ratio of Volume(infusion): Volume(distribution) – ranges between 1:3 to 1:3.5
  • OS is promising but remains to be reviewed in the context of available molecular data for each patient and also in the setting that some patients may have undergone re-irradiation
  • Several patients progressed outside the treatment field, suggesting that either larger infusion volumes or combination with systemic therapy should be considered in future trials
  • Ongoing assessment of imaging parameters as well as QOL assessments


  • Nalin Gupta
  • Cassie Kline
  • Carly Hoffmann
  • Javier Villanueva-Meyer
  • Annette Molinaro
  • Shannon Raber
  • Erin Bonner
  • Javad Nazarian
  • Mariella Filbin
  • Michael Prados
  • Families and patients
  • Funding sources:
    • The Pediatric Brain Tumor Foundation, DIPG Collaborative; Midatech Inc.
    • Midatech as a sponsor had no involvement in study analysis