380TiP - A phase I/II dose-escalation and expansion cohort study of intracerebroventricular radioimmunotherapy using ¹⁷⁷Lu-DTPA-omburtamab in pediatric and adolescent patients with recurrent or refractory medulloblastoma

Background

Medulloblastoma represents 20% of all pediatric brain tumors. Recurrent/refractory medulloblastoma is particularly challenging, with no standard of care and poor treatment outcomes. The B7-H3 receptor is an attractive target for radioimmunotherapy as it is overexpressed on the cell surface of >96% of medulloblastomas. Omburtamab is a monoclonal antibody that specifically binds to B7-H3 and can be radiolabeled allowing targeted delivery of therapeutic radiation to tumor cells. Intracerebroventricular administration of ¹³¹I-omburtamab is currently under study in patients (pts) with neuroblastoma and CNS/leptomeningeal metastases and has received breakthrough designation by the FDA. The trial described here (Study 301) is a first-in-human study to evaluate the tolerability and safety of ¹⁷⁷Lu-DTPA-omburtamab in pts with recurrent/refractory medulloblastoma.

Trial design

Study 301 is an open-label phase I/II study. Part 1 is a dose-escalation phase to be conducted at ∼8 sites (US/Europe) with a primary objective of identifying the maximum tolerated dose and/or recommended phase II dose for Part 2 (RP2D). It will follow a 3+3 design (except 1^st dose, which is limited to 1+2 pts) with pts receiving up to two 5-week cycles of ¹⁷⁷Lu-DTPA-omburtamab. Part 2 is a cohort-expansion phase at ∼11 sites (US/Europe) with pts receiving up to five 5-week cycles of treatment at the RP2D from Part 1. The primary objective of Part 2 is to establish the safety of repeat doses of ¹⁷⁷Lu-DTPA-omburtamab. Additional objectives of Parts 1/2 include the evaluation of absorbed radiation doses, PK profile, investigator-assessed response, duration of response, progression-free survival, and overall survival. Up to 25 pts are expected to participate in Part 1 and 24 in Part 2. Key inclusion criteria include age 3-19 years; histologically confirmed medulloblastoma; available molecular classification; recurrent/refractory to frontline therapy; Lansky or Karnofsky score of 50-100, acceptable hematological status and liver and kidney function, and a life expectancy of >3 months.

Clinical trial identification

NCT04167618.

Editorial acknowledgement

Under direction and guidance from the authors, medical writing support was provided by Michael Malia, PhD, an employee of Y-mAbs Therapeutics.

Legal entity responsible for the study

Y-mAbs Therapeutics, Inc.

Funding

Y-mAbs Therapeutics, Inc.

Disclosure

M. Düring: Financial Interests, Personal, Full or part-time Employment: Y-mabs Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Y-mabs Therapeutics, Inc. C.L. Lind: Financial Interests, Personal, Full or part-time Employment: Y-mabs Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Y-mabs Therapeutics, Inc. J.R. Nielsen: Financial Interests, Personal, Full or part-time Employment: Y-mabs Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Y-mabs Therapeutics, Inc. All other authors have declared no conflicts of interest.