FDA Approves Naxitamab-gqgk for Relapsed/Refractory High-Risk Neuroblastoma

The FDA has granted an accelerated approval to naxitamab-gqgk (Danyelza) for use in combination with granulocyte-macrophage colony-stimulating factor as a treatment for pediatric patients 1 year of age and older and adult patients with relapsed/refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior treatment.¹

The decision is supported by clinical evidence from 2 studies in patients with high-risk neuroblastoma with refractory/relapsed disease.

“Today is an important day for children living with refractory/relapsed high-risk neuroblastoma,” said Thomas Gad, founder, chairman and president, of Y-mAbs, the developer of naxitamab. “It’s very exciting to see this treatment go from being an experimental therapy used at my daughter’s bedside to now being FDA approved. On behalf of Y-mAbs, I want to thank all the patients and physicians who took part in our clinical trials and our scientific partner, Memorial Sloan Kettering, for helping us achieve this goal.”

Naxitamab is a GD2-directed monoclonal antibody, which is highly expressed in various neuroectoderm-derived tumors and sarcomas. Naxitamab is administered to patients 3 times per week in an outpatient setting and is repeated every 4 weeks.

Initial results from the Study 12-230 trial (NCT01757626) had been presented at the 2019 International Society of Pediatric Oncology Annual Congress.² At the meeting, data from several subsets of patients who received the agent were released.

In 28 patients with primary refractory high-risk neuroblastoma, the ORR as 78% and the 2-year PFS rate was 50%. In a subset of 35 patients with relapsed neuroblastoma resistant to salvage therapy, the ORR was 37% and the 2-year PFS rate was 36%. In 44 patients with high-risk neuroblastoma in second or later complete remission and no evidence of disease, naxitamab was given in combination with GM-CSF as maintenance therapy; this resulted in a 2-year PFS rate of 52%.

Findings from a trial (NCT03363373) detailed in a poster presentation that had recently been presented at the 2020 ASCO Virtual Meeting showed that treatment with the agent in 24 patients with relapsed/refractory high-risk neuroblastoma led to a high complete response (CR) rate of 71% (95% CI, 49%-87%) and an overall objective response rate (ORR) of 79 (95% CI, 58%-93%).³

Of 16 patients who were primary refractory, the ORR with naxitamab was 88% (95% CI, 62%-98%) and the CR rate was 81% (95% CI, 54%-96%). Of 8 patients who had an incomplete response to salvage treatment, the ORR and CR rates were 63% (95% CI, 24%-91%) and 50% (95% CI, 16%-84%), respectively. Thirteen of 14 patients who had bone marrow disease at baseline experienced bone marrow clearance.

The median progression-free survival (PFS) was 42 weeks (95% CI, 26—not estimable), and the median follow-up time in patients evaluable for efficacy was 30 weeks.

With regard to safety, 88% of patients experienced at least 1 related treatment-emergent adverse event (TEAE) that was grade 3/4 in severity; these events included general disorders and administration site conditions (72%), pain (72%), vascular disorders (60%), hypotension (60%), respiratory, thoracic, and mediastinal disorders (44%), skin and subcutaneous tissue disorders (40%), and urticaria (40%), among others.

Six serious related TEAEs were reported in 5 patients: anaphylactic reaction (n = 4), pyrexia (n = 1), and respiratory depression (n = 1).

The accelerated approval is contingent on the results of the confirmatory, ongoing Study 201 trial. The study will enroll a minimum of 80 patients.

Reference

1. FDA Approves Y-mAbs’ DANYELZA® (naxitamab-gqgk) for the Treatment of Neuroblastoma. News release. Y-mAbs. November 25, 2020. Accessed November 25, 2020. https://bit.ly/3nVyHGl.
2. Y-mAbs announces naxitamab update. News release. Y-mAbs Therapeutics, Inc. October 25, 2019. Accessed June 2, 2020. bit.ly/2XrflyG.
3. Mora J, Chan GC-F, Morgenstern DA, et al. Naxitamab, a new generation anti-GD2 monoclonal antibody (mAb) for treatment of relapsed/refractory high-risk neuroblastoma (HR-NB). J Clin Oncol. 2020;38(suppl 15):10543. doi:10.1200/JCO.2020.38.15_suppl.1054.