Omblastys (131I-omburtamab) / SERB Pharmaceuticals, Memorial Sloan-Kettering Cancer Center, United Therapeutics Corp - LARVOL DELTA

A Study of the Drug I131-Omburtamab in People With Desmoplastic Small Round Cell Tumors and Other Solid Tumors in the Peritoneum (clinicaltrials.gov) - P2 | N=31 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Febrile Neutropenia • Oncology • Peritoneal Cancer • Soft Tissue Sarcoma • Solid Tumor

From Seeing to Healing: The Clinical Potential of Radiotracers in Pediatric Neuro-Oncology. (PubMed, Cancers (Basel)) - "Additionally, peptide receptor-based radiotracers, such as 68Ga-DOTATATE and 177Lu-DOTATATE, are already used for both diagnostic purposes and targeted radiotherapy, particularly in neuroblastomas and gliomas. Antibody-based radiotracers like 131I-omburtamab, targeting B7-H3, are emerging as promising tools for addressing difficult-to-treat tumors such as diffuse midline glioma. Collectively, these advances provide new hope for children afflicted by these devastating malignancies, offering promising solutions for more specific and precise diagnosis and, additionally, for more effective, personalized, and less toxic tumor therapies."

Journal • Review • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Medulloblastoma • Neuroblastoma • Oncology • Pediatrics • Solid Tumor

A Study of the Drug I131-Omburtamab in People With Desmoplastic Small Round Cell Tumors and Other Solid Tumors in the Peritoneum (clinicaltrials.gov) - P2 | N=31 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | N=55 ➔ 31 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Febrile Neutropenia • Hematological Disorders • Oncology • Peritoneal Cancer • Soft Tissue Sarcoma • Solid Tumor

A Study of the Drug I131-Omburtamab in People With Desmoplastic Small Round Cell Tumors and Other Solid Tumors in the Peritoneum (clinicaltrials.gov) - P2 | N=55 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Jul 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • Febrile Neutropenia • Hematological Disorders • Oncology • Peritoneal Cancer • Soft Tissue Sarcoma • Solid Tumor

Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease. (PubMed, EJNMMI Res) - P2/3 | "131I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402 ."

Journal • Oncology • Pediatrics • Solid Tumor

LONG-TERM REMISSION OF RECURRENT METASTATIC MEDULLOBLASTOMA WITH 131-I OMBURTAMAB-8H9 AND VISMODEGIB (ASPHO 2024) - "She received craniospinal radiation 2340 cGy with a boost to the posterior fossa, followed by 5 cycles of chemotherapy as per the SJMB trial with cisplatin, cyclophosphamide and vincristine...MRI showed leptomeningeal disease in the spine for which she completed 2 cycles of topotecan/cytoxan with intra Ommaya methotrexate, with stabilization of the disease...Two months later, an MRI demonstrated mets isolated to the foramen magnum prompting radiation to that lesion, started on 5 oral metronomic antiangiogenic chemotherapy plus Avastin. Chemotherapy resumed with temozolomide/irinotecan plus intrathecal etoposide and thiotepa. Nonetheless, an MRI demonstrated progressive leptomeningeal disease in the brain requiring cranial irradiation with oral etoposide... Recurrent primary CNS tumors have few curative treatment options. Medulloblastomas continue to present treatment challenges for care providers. Close long-term monitoring is required to ensure long-term spontaneous..."

Clinical • Metastases • Brain Cancer • CNS Disorders • CNS Tumor • Embryonal Tumor • Medulloblastoma • Musculoskeletal Pain • Oncology • Pain • Pediatrics • Solid Tumor • PTCH1

B7-H3 Inhibitors in Oncology Clinical Trials: A Review. (PubMed, J Immunother Precis Oncol) - "Particularly promising treatments are enoblituzumab for prostate cancer, 131I-omburtamab for central nervous system malignancies, and HS-20093 for small-cell lung cancer but further studies are warranted. These data will be telling of the efficacy of B7-H3 inhibitors in both hematologic and solid malignancies. This study aimed to compile available results of B7-H3 inhibitors in oncology clinical trials."

Journal • Review • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Hematological Disorders • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • CD276

Trial 101: 131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases (clinicaltrials.gov) - P2/3 | N=52 | Terminated | Sponsor: Y-mAbs Therapeutics | Trial completion date: Dec 2026 ➔ Jun 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2026 ➔ Jun 2023; Corporate business decision. Not due to safety or efficacy concerns.

Trial completion date • Trial primary completion date • Trial termination • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

Laser interstitial thermal therapy as a radiation-sparing approach for central nervous system tumors in children with cancer predisposition syndromes: report of a child with Li-Fraumeni syndrome. Illustrative case. (PubMed, J Neurosurg Case Lessons) - "Alternatives to mutagenic therapies for brain tumors should be explored for patients with CPS. LITT paired with imaging surveillance is a logical strategy to ensure durable outcomes and mitigate treatment-related secondary neoplasms."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Metabolic Disorders • Oncology • Pediatrics • Solid Tumor • TP53

131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma (clinicaltrials.gov) - P2 | N=62 | Active, not recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Oct 2029 ➔ Oct 2030 | Trial primary completion date: Oct 2028 ➔ Oct 2029

Trial completion date • Trial primary completion date • Brain Cancer • Ependymoma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • CD276

Radiolabeled MAB Therapy in Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer (clinicaltrials.gov) - P1 | N=177 | Terminated | Sponsor: Y-mAbs Therapeutics | N=120 ➔ 177 | Active, not recruiting ➔ Terminated; Corporate business decision. No safety or efficacy concerns.

Enrollment change • Metastases • Trial termination • Brain Cancer • CNS Tumor • Neuroblastoma • Oncology • Sarcoma • Solid Tumor

Intraperitoneal RIT With 131I-8H9 for Pts With DSRCT and Other Solid Tumors Involving the Peritoneum (clinicaltrials.gov) - P1 | N=54 | Terminated | Sponsor: Y-mAbs Therapeutics | Active, not recruiting ➔ Terminated; Corporate business decision. Not due to safety or efficacy concerns

Trial termination • Adrenal Cortex Carcinoma • Oncology • Peritoneal Cancer • Soft Tissue Sarcoma • Solid Tumor • CD34

131I-omburtamab Delivered by Convection-Enhanced Delivery in Patients With Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Y-mAbs Therapeutics | N=36 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

Trial 101: 131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases (clinicaltrials.gov) - P2/3 | N=52 | Active, not recruiting | Sponsor: Y-mAbs Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor

Intraperitoneal Radioimmunotherapy With 131I-8H9 for Patients With Desmoplastic Small Round Cell Tumors and Other Solid Tumors Involving the Peritoneum (clinicaltrials.gov) - P1 | N=54 | Active, not recruiting | Sponsor: Y-mAbs Therapeutics | Trial completion date: Sep 2022 ➔ Sep 2023

Trial completion date • Adrenal Cortex Carcinoma • Oncology • Peritoneal Cancer • Soft Tissue Sarcoma • Solid Tumor • CD34

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 (ESMO-IO 2022) - P2/3 | "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 • Late-breaking abstract • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • CD276

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma. (PubMed, J Neurooncol) - "For patients with medulloblastoma, remission at time of cRIT was associated with significantly improved survival outcomes. Relapses are often multifocal, particularly in the setting of measurable disease at cRIT initiation. EBRT is a promising tool to achieve NED status at cRIT initiation, with no cases of radiation necrosis."

Journal • Brain Cancer • Ependymoma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

Kirby McInerney LLP Announces the Filing of a Securities Class Action on Behalf of Y-mAbs Therapeutics, Inc. (YMAB) Investors (Businesswire) - "The law firm of Kirby McInerney LLP announces that a class action lawsuit has been filed in the U.S. District Court for the Southern District of New York on behalf of those who acquired Y-mAbs Therapeutics, Inc. ('Y-mAbs') (NASDAQ: YMAB) securities during the period from October 6, 2020 through October 28, 2022 (the 'Class Period'). Investors have until March 20, 2023 to apply to the Court to be appointed as lead plaintiff in the lawsuit....The action alleges that throughout the Class Period, Y-mAbs misrepresented to investors that, pursuant to a series of meetings and other communications between Y-mAbs and the FDA, that progress was being made that would align with the FDA's requirement to demonstrate substantial evidence of effectiveness, sufficient for approval of omburtamab....Further, Y-mAbs failed to advise investors that it had elected to submit the March 31, 2022 BLA prior to reaching agreement with the FDA on the content of the application."

Corporate lawsuit • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma (clinicaltrials.gov) - P2 | N=62 | Active, not recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Jul 2030 ➔ Oct 2029 | Trial primary completion date: Jul 2027 ➔ Oct 2028

Trial completion date • Trial primary completion date • Brain Cancer • Ependymoma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • CD276

Y-mAbs Announces Restructuring Plan and Provides Financial Outlook Following Complete Response Letter from FDA (GlobeNewswire) - "Y-mAbs Therapeutics...announced a strategic restructuring plan designed to extend its cash runway and prioritize resources on the commercialization and potential label extension of DANYELZA and development of the SADA (Self-Assembly DisAssembly ('SADA') PRIT 2-STEP) technology platform....The Company has assumed a deprioritization of the omburtamab program, including all indications, in designing its restructuring plan and in its estimates for 2023. In addition, the Company plans to deprioritize other pipeline programs, including activities relating to GD2-GD3 Vaccine and CD33 bispecific antibody constructs....'We anticipate a Type A meeting with the FDA in January 2023 to discuss the future of omburtamab'....Targeting an IND submission in Q2 2023 for CD38-SADA construct against non-Hodgkin's lymphoma to potentially validate SADA in blood cancers....Estimated DANYELZA net product revenues for the 2023 fiscal year are expected to be between $60-65 million."

FDA event • IND • Pipeline update • Sales projection • Neuroblastoma • Oncology • Solid Tumor

The CHMP has Adopted a Negative Opinion for Omburtamab for the Treatment of CNS/LM Metastasis from Neuroblastoma in Europe (GlobeNewswire) - "Y-mAbs Therapeutics...announced that the European Committee for Medicinal Products for Human use ('CHMP') has adopted a negative opinion recommending a refusal of the marketing authorization for omburtamab for the treatment of CNS/leptomeningeal metastasis from neuroblastoma in Europe."

European regulatory • Neuroblastoma • Oncology • Solid Tumor

Y-mAbs Announces Complete Response Letter for Omburtamab Biologics License Application (GlobeNewswire) - "Y-mAbs Therapeutics...announced that the U.S. Food and Drug Administration ('FDA') has issued a complete response letter ('CRL') for the Biologics License Application ('BLA') for the investigational medicine 131I-omburtamab ('omburtamab') for the treatment of CNS/leptomeningeal metastasis from neuroblastoma. The letter indicates that the FDA completed the review of the application and determined that it is unable to approve the BLA in its current form. This is consistent with the outcome of the Oncologic Drugs Advisory Committee Meeting in October. The CRL includes a recommendation for meeting with the agency to discuss adequate and well-controlled trial design....Y-mAbs is assessing the implications of the CRL and its plans for the omburtamab program."

FDA event • Neuroblastoma • Oncology • Solid Tumor

Y-mAbs Announces Outcome of FDA Advisory Committee Meeting on Omburtamab (GlobeNewswire) - "Y-mAbs Therapeutics...announced the outcome of the meeting of the U.S. Food and Drug Administration ('FDA') Oncologic Drugs Advisory Committee ('ODAC'), which reviewed investigational 131I-omburtamab ('omburtamab') for the treatment of CNS/leptomeningeal metastasis from neuroblastoma. The committee voted 16 to 0 that the Company had not provided sufficient evidence to conclude that omburtamab improves overall survival....ODAC reviewed data from omburtamab’s clinical development program with a focus on study 03-133 (a pivotal phase 1 study) and study 101 (a pivotal phase 2 study) as well as the historical control group."

ODAC • Brain Cancer • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

FDA Panel: All Thumbs Down for Antibody to Treat Metastatic Neuroblastoma (MedPageToday) - "'The panel does not feel that the applicant has met the criteria needed to prove an overall survival benefit,' said Christopher Lieu, MD... 'The panel would like to see increased response, obviously, if possible, and an improved comparator, and potentially even more robust preclinical data.'"

Media quote

Y-mAbs Announces Pivotal Data for Omburtamab (GlobeNewswire) - P2/3 | N=50 | NCT03275402 | Sponsor: Y-mAbs Therapeutics | "Y-mAbs Therapeutics...announced clinical data on the Company’s product candidate OMBLASTYS® (131I-omburtamab) for the treatment of CNS/leptomeningeal metastasis from neuroblastoma. Data was presented by Dr. Kim Kramer from Memorial Sloan Kettering Cancer Center ('MSK') at the International Society of Pediatric Oncology ('SIOP') Annual Congress....The results showed a twelve-month overall survival ('OS') of 73.5%, with a median follow-up of 25 months. Further, the interim results showed an objective response rate ('ORR') of 31.3% in the patients with measurable disease after central review based on Response Assessment in Neuro-Oncology ('RANO') criteria and European Association of Neuro-Oncology ('EANO')/European Society for Medical Oncology ('ESMO') criteria, and that a total of 75.0% of the patient with measurable disease achieved disease control."

P2/3 data • Brain Cancer • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor