Reduction in curie score in neuroblastoma patients treated with naxitamab.

Abstract

10042 Background: Patients with high-risk neuroblastoma (HR-NB) most frequently present with metastases in the bone marrow (BM; 70–89%) and bone (56–65%). Approximately 15% of HR-NB patients will be refractory to induction therapy and 50% will relapse. Naxitamab is a humanized GD2-binding monoclonal antibody approved in the US with granulocyte-macrophage colony-stimulating factor (GM-CSF) for treatment of patients ≥1-yr with refractory/relapsed (R/R) HR-NB in the bone or BM with partial response, minor response, or stable disease to prior therapy. Curie Score (CS) is an important tool for assessing extent of disease and treatment response. The reduction in CS by baseline disease status, i.e., refractory or relapsed, from Trial 201 pre-specified interim analysis (data cut-off 31-dec-2021) is reported. Methods: Ongoing Trial 201 (phase II, NCT03363373) evaluates naxitamab+GM-CSF in patients with R/R HR-NB with residual disease limited to bone/BM. Soft tissue and actively progressing disease were addressed prior to enrollment. Naxitamab was administered (intravenously) at 3mg/kg/day over 30-60 min on Days 1/3/5 with GM-CSF (subcutaneous) on Days -4 to 5 at 4-week cycles. 123I-MIBG scans were used to assess CS and treatment response according to INRC criteria per independent review. Results: Interim analysis included 52 (efficacy group) and 74 (safety) patients. The primary endpoint achieved an overall response rate (ORR) of 50% [95% CI: 35.8- 64.2] with complete response rate (CR) of 38%. A summary of changes in overall CS by disease status is reported in the table. Median change in CS from baseline to end of treatment (EOT) was −1 across refractory and relapsed subgroups and ranged from −18 to 18. Baseline CS (≤ 2 vs. ≥3) did not affect the safety profile. The most common adverse events were pain, hypotension, urticaria, and bronchospasm. The frequency of Grade 3 or higher and serious related adverse events was lower for patients with refractory vs. relapsed disease, i.e. lower rates of severe hypotension (51% vs. 68%), increased ALT (0% vs. 14%), and hypoxia (3% vs. 16%). Conclusions: Clinically meaningful reductions in CS were seen in patients regardless of baseline disease status (relapsed or refractory HR-NB). Baseline CS did not affect the safety profile. Refractory patients had a lower frequency of severe and serious related adverse events.. Clinical trial information: NCT03363373 . [Table: see text]