US FDA approves naxitamab to treat neuroblastoma

US FDA approves naxitamab to treat neuroblastoma

A combinational therapy including naxitamab-gqgk (Danyelza) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has been approved by the US FDA for patients aged 1 year and older with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a response or stable disease after prior therapy.

Naxitamab is a humanized, monoclonal antibody that targets the ganglioside GD2, which is highly expressed in various neuroectoderm-derived tumours and sarcomas.

Neuroblastoma is a cancer that develops from immature nerve cells found in several areas of the body. Neuroblastoma most commonly arises in and around the adrenal glands, which have similar origins to nerve cells and is located on the kidneys.

The approval was based on results from two single-arm, open-label trials in patients with relapsed or refractory neuroblastoma in the bone or bone marrow: the multicentre study 201 and the single-centre study. Patients with progressive disease after their most recent therapy were excluded from the trials.

In the trials, patients received naxitamab at 3 mg/kg dose on days 1, 3 and 5 of each four-week cycle, in combination with GM-CSF at 250 mcg/m2 dose from 4 days prior to the treatment and at 500 mcg/m2 per day on days 1-5.

At the investigator’s discretion, patients were permitted to receive preplanned radiation to the primary disease site in Study 201 and radiation therapy to nontarget bony lesions or soft tissue disease in Study 12-230. The main efficacy outcome measures were confirmed overall response rate (ORR) per the revised International Neuroblastoma Response Criteria and duration of response (DOR).

Among 22 patients treated in Study 201, the overall response rate (ORR) was 45%, and 30% of responders had a duration of response (DOR) of at least six months. Among 38 patients treated in Study 12-230, the ORR was 34% with 23% of patients having a DOR of at least six months. For both trials, responses were observed in either the bone, bone marrow or both.

Naxitamab can cause adverse side effects including infusion-related reactions and neurotoxicity, including severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome.

To mitigate these risks, patients should receive premedication before each naxitamab infusion and be closely monitored during and for at least two hours after completion of each infusion. Based on the severity of such reactions, rate reductions and/or temporary or permanent discontinuation of naxitamab may be required.