The FDA has granted an orphan drug designation and rare pediatric disease designation to the bispecific antibody nivatrotamab for the treatment of patients with neuroblastoma, according to an announcement from Y-mAbs Therapeutics, Inc.1
“We are very pleased with the orphan drug designation for nivatrotamab, as this potentially would give us 7 years of market exclusivity upon market approval,” Thomas Gad, founder, chairman, and president of Y-mAbs, stated in a press release. “The rare pediatric disease designation makes us eligible for a Priority Review Voucher (PRV) upon potential approval of the biologics license application for this rare pediatric cancer. Among our leading compounds, 4 now have rare pediatric disease designations, and this designation further increases our chances of ultimately receiving multiple PRVs.”
Nivatrotamab is the first T-cell–engaging antibody to use the BiClone format to enter human clinical trials, according to the company.2 The BiClone format uses an IgG-scFv format to augment tumor binding and T-cell recruitment, while reducing the risk of non-specific T-cell engagement. The agent was developed by investigators at Memorial Sloan Kettering Cancer Center (MSKCC) and is exclusively licensed to Y-mAbs.
Data from preclinical studies examining the agent showed that it led to over 1000-fold greater potency over conventional anti-GD2 IgG antibodies.
The agent is currently under examination in a phase 1/2 study (NCT03860207), which is being conducted by investigators from MSKCC.3 In the trial, investigators are evaluating the safety of the agent in patients with relapsed/refractory neuroblastoma, osteosarcoma, and other solid tumor cancers. The trial is estimated to enroll 30 participants.
To be considered for inclusion on the phase 1 portion of the trial, patients must have received a diagnosis of neuroblastoma defined by international criteria and confirmed by the MSKCC Department of Pathology. With regard to tumors other than neuroblastoma or osteosarcoma, only patients with GD2-positive tumors can participate; as such, those with melanoma, desmoplastic small round cell tumors, retinoblastoma, medulloblastoma, and soft tissue sarcomas, are eligible.
Moreover, patients with neuroblastoma must be refractory to chemotherapy or have relapsed, high-risk disease. Those with osteosarcoma must have relapsed or refractory disease following standard systemic chemotherapy. Patients with non-neuroblastoma or non-osteosarcoma tumors who have GD2-positive disease, must have relapsed or refractory disease that is resistant to standard therapy in order to participate.
For the phase 2 portion of the trial, patients with neuroblastoma must be refractory to chemotherapy or have relapsed high-risk disease to be eligible for group 1. Additionally, the diagnosis of neuroblastoma must be defined by international criteria. For group 2, patients need to have a diagnosis of high-grade osteosarcoma per histopathology. Patients must have relapsed or refractory disease following standard systemic chemotherapy.
Overall, patients must be 1 year of age or older, have had previous exposure to anti-GD2 antibodies with a human anti-human antibody (HAHA) titer of less than 1300U/mL. Patients also needed to have acceptable hematopoietic function.
Patients in complete remission, who have severe major organ dysfunction, hematologic and active central nervous systemic (CNS) malignancies, active life-threatening infection, a history of autoimmune disease with potential CNS involvement or current autoimmune disease, are not eligible for inclusion. Patients who received chemotherapy or immunotherapy within 3 weeks before starting the study cannot participate.
In the trial, patients will receive nivatrotamab intravenously over approximately 1 to 3 hours on days 1 and 8 of each treatment cycle. In cycle 1, blood will be collected for pharmacokinetic analysis. The primary end point of the trial is maximum-tolerated dosage, which will be defined as the dose at which the toxicity rate does not exceed an acceptable threshold of 15%.
“We are very pleased by this recognition by the FDA, and plan to expand the ongoing study with nivatrotamab into 2 separate phase 2 arms in neuroblastoma and osteosarcoma, respectively, as well as a separate phase 2 multicenter study in small cell lung cancer,” Claus Moller, MD, PhD, chief executive officer of Y-mAbs, added in the release. “We expect to submit an investigational new drug [application] for the lung cancer study during the fourth quarter of 2020, and we are thrilled to widen nivatrotamab’s clinical reach to include adult indications.”
1. Y-mAbs’ nivatrotamab for the treatment of patients with neuroblastoma granted orphan drug designation and rare pediatric disease designation by FDA. News release. October 7, 2020. Accessed October 7, 2020. https://bit.ly/3lt1hhj.
2. Our pipeline. Y-mAbs Therapeutics, Inc. Accessed October 7, 2020. https://bit.ly/3d8MFAv.
3. Study of the safety and efficacy of humanized 3F8 bispecific antibody (Hu3F8-BsAb) in patients with relapsed/refractory neuroblastoma, osteosarcoma, and other solid tumors. ClinicalTrials.gov. Updated November 8, 2019. Accessed October 7, 2020. https://www.clinicaltrials.gov/ct2/show/NCT03860207.
This article was originally published on OncLive as, "FDA Grants Nivatrotamab Orphan Drug Status for Pediatric Neuroblastoma."