Irinotecan, temozolomide and naxitamab plus GM-CSF (HITS) and naxitamab plus GM-CSF and ifosfamide, carboplatin, etoposide (NICE) for patients with relapsed or refractory high-risk neuroblastoma: A single center, open-label phase 2 clinical trial.

10039 Background: Patients with relapsed/refractory (R/R) high-risk neuroblastoma (HR-NB) have a poor prognosis, underscoring the need to explore new therapies. In this single institution, Phase 2 clinical trial (EudraCT 2020-000538-17), we evaluated the safety and efficacy of HITS and Naxitamab (NAX) in combination with ICE (NICE) in patients (pts) with R/R HR-NB with incomplete response (partial response (PR), minor response (MR), or stable disease (SD)) to HITS. Methods: Eligible pts received 2-4 cycles of HITS. Patients achieving a complete response (CR as per 2017 INRC) to HITS after 2 or 4 cycles had the CR consolidated with 5 cycles of NAX+GM-CSF. Patients with an incomplete response to HITS transitioned to NICE (up to 4 cycles) and those with progressive disease (PD) discontinued. CRs to NICE were consolidated with 5 cycles of NAX+GM-CSF. HITS consisted of Irinotecan 50 mg/m2/day IV from day 1-5 concurrently with temozolomide 150 mg/m2/day orally; NAX 2.25mg/kg IV on days 2, 4, 9 and 11; and GM-CSF 250 mcg/m2/day SC on days 7-11. NICE cycles consisted of NAX 2.25 mg/kg IV on days 2, 4, 9 and 11; GM-CSF 250 mcg/m2/day SC on days 7-11; ifosfamide 1.5 gr/m2/day IV from day 1-3 concurrent with etoposide 100 mg/m2/day IV and carboplatin 400 mg /m2/day IV on day 1. HITS/NICE cycles were administered out/inpatient, respectively. NAX was infused according to the Step-Up protocol. Treatment cycles were repeated every 4 weeks. Follow-up continued quarterly after end of treatment visit for up to 3 years. Results: From September 2020 until December 2022, 47 patients were screened and 34 enrolled. Of the 34 pts, 2 (5.9%) had primary refractory and 32 (94.1%) relapsed refractory disease. Prior treatments included chemotherapy (34; 100%); surgery (29; 85.3%); radiotherapy (17; 50%); autologous stem cell transplant (11; 32.4%); and anti-GD2 immunotherapy (15; 44.1%. 11 NAX and 4 dinutuximab beta). Of the 19 pts with an incomplete response after HITS, 13 (68.4%) received at least one cycle of NICE, and 5 completed all therapy. For HITS, the objective response rate (ORR) was 50% and best overall response (OR) was CR = 8 (23.5%); PR = 9 (26.5%); SD = 10 (29.4%); and PD = 7 (20.6%). For NICE ORR was 53.8% and OR: CR = 2 (15.4%); PR = 5 (38.5%); and SD = 6 (46.2%). No treatment related deaths occurred. All pts receiving NICE experienced grade 3-4 AEs (most frequent were pain (29.5%); urticaria (27.4 %); and thrombocytopenia (6.8%)), one leading to treatment discontinuation. Conclusions: Our clinical trial results suggest different chemotherapy combinations with naxitamab have the potential to rescue patients with R/R HR-NB. No unexpected toxicities were found when combining NAX with different chemotherapeutic agents. Clinical trial information: EudraCT 2020-000538-17 .