LBA3 - Compartmental Radioimmunotherapy (cRIT) 131I-OMBURTAMAB in Patients with Neuroblastoma (NB) Central Nervous System (CNS) and/or Leptomeningeal (LM) Metastases: Updated Results from Pivotal Trial 101

Background

Up to 10% of patients (pts) with NB develop CNS/LM metastases, with recently reported 1-year overall survival rate of ∼25% (+/-6%). OMB is a murine monoclonal antibody that binds B7H3, a transmembrane glycoprotein highly expressed in NB and other solid tumors. Iodine-131-labeled OMB is administered into the CSF via indwelling intraventricular Ommaya reservoir to achieve a high cerebrospinal fluid (CSF):blood absorbed dose ratio. We report an updated analysis of Trial 101: ¹³¹I-OMB in pts with NB CNS/LM metastases.

Methods

Trial 101 (NCT03275402) is a phase-2/3, single-arm, global trial in pts 0-18 years old with radiographically and/or histologically confirmed CNS/LM NB. As of 31 March 2022, 50 pts were included in the efficacy and safety analysis. Treatment consisted of 2 doses of up to 50 mCi ¹³¹I-OMB (age-based) administered at least 4-weeks apart. A dosimetry dose of 2 mCi ¹³¹I-OMB was administered to 26 out of the 50 patients 1 week before the first treatment dose. The primary endpoint was CNS/LM progression-free survival (PFS) at 6 months (mo). Secondary endpoints were overall survival (OS) at 12 mo (from first treatment dose) and independently assessed objective response rate (ORR) at 6 mo. CSF:blood absorbed dose ratio and absorbed doses to normal organs were assessed. Long-term follow-up is ongoing.

Results

The estimated CNS/LM PFS at 6 mo was 75% (95% CI 61-85); 12-mo OS was 79% (95% CI 64-89). ORR was 35% (7 / 20 pts with measurable disease at baseline) with complete response (CR) of 25%. Disease control rate (CR+PR+SD) was 70%. Most frequent grade 3-4 adverse events were myelosuppression. Four pts had intracranial hemorrhage; 2 had chemical meningitis (prior to implementing high-dose corticosteroid pre-medication). The CSF:blood absorbed dose mean ratio was 1.219 Gy:0.016 Gy, or ∼76 times higher in the CSF compared to the blood, following the dosimetry dose. Liver, brain, bladder showed highest organ absorbed doses.

Conclusions

These results suggest that ¹³¹I-OMB has an acceptable dosimetry, manageable safety profile, and may provide survival and clinical benefit (OS, CNS/LM PFS, ORR) for pts with NB CNS/LM metastases.

Clinical trial identification

NCT03275402.

Legal entity responsible for the study

Y-mAbs Therapeutics.

Funding

Y-mAbs Therapeutics.

Disclosure

J. Mora, M. Bear: Financial Interests, Personal, Advisory Role: Y-mabs Therapeutics. K. Streby: Financial Interests, Personal, Advisory Role: Y-mabs Therapeutics, Illumina Radiopharmaceuticals, LLC. H. Sano: Financial Interests, Personal, Other, Honoraria: Sanofi, Chugai, Bayer, Kyowa Kirin, JCR Pharma. A. Marachelian: Financial Interests, Personal, Other, Honoraria: Y-mabs Therapeutics; Financial Interests, Personal, Advisory Board: Y-mabs Thereapeutics; Financial Interests, Personal and Institutional, Research Grant: Y-mabs Therapeutics, United Therapeutics, Pfizer, Jubilant Therapeutics. K. Nysom: Financial Interests, Personal, Other, Honoraria: Y-mabs Therapeutics; Financial Interests, Personal, Advisory Role: Y-mabs Thereapeutics, Bayer, EUSA Pharma, Lilly; Financial Interests, Personal, Other, Teaching: Y-mabs Therapeutics, Bayer. N. Pandit-Taskar: Financial Interests, Personal, Advisory Role: Actinium Pharmaceuticals Inc., Illumina, ImaginAb, Medimmune Llc/AstraZeneca, Progenics Pharmaceuticals; Financial Interests, Personal and Institutional, Research Grant: Bayer, Bristol Myers Squibb, Clarity Pharma Ltd, ImaginAb, Janssen Pharmaceuticals, Regeneron Pharmaceuticals, Y-mAbs Therapeutics. P. Zanzonico: Financial Interests, Personal, Advisory Role: Radionetics Oncology; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Invited Speaker, Intellectual property license: Y-mabs Thereapeutics. S. Fabricius: Financial Interests, Personal, Stocks/Shares: Y-mabs Therapeutics; Financial Interests, Personal, Full or part-time Employment: Y-mabs Thereapeutics. M. During: Financial Interests, Personal, Full or part-time Employment: Y-mabs Therapeutics; Financial Interests, Personal, Stocks/Shares: Y-mabs Thereapeutics. J.R. Nielsen: Financial Interests, Personal, Full or part-time Employment: Y-mabs Therapeutics; Financial Interests, Personal, Stocks/Shares: Y-mabs Thereapeutics. K. Kramer: Financial Interests, Personal, Other, Intellectual Property Rights: Y-mabs; Financial Interests, Personal, Stocks/Shares: Y-mabs; Financial Interests, Personal, Other, Provision of services: Y-mabs. All other authors have declared no conflicts of interest.