Naxitamab-based chemoimmunotherapy for resistant high-risk neuroblastoma: Results of "HITS" phase II study.

• DOI: 10.1200/jco.2022.40.16_suppl.10028
• Publication Date: 2022-06-06T17:31:24Z
• Authors: Shakeel Modak; Brian H. Kushner; Audrey Mauguen; Alicia Castañeda; Amalia Varo; Maite Gorostegui; Juan Pablo Muñoz; Vicente Santa-Maria; Ellen M. Basu; Fiorella Iglesias...; Neeta Pandit-Taskar; Nai-Kong V. Cheung; Jaume Mora
• Keywords: Temozolomide; Dacarbazine; Clinical endpoint; Chemoimmunotherapy

10028 Background: Chemoresistant disease is an obstacle for cure of high-risk neuroblastoma (HR-NB). Anti-GD2 monoclonal antibodies (MoAb) dinutuximab and naxitamab in combination with cytokines are FDA-approved to consolidate remission chemorefractory osteomedullary HR-NB, but responses progressive (PD) rare. We investigated the Humanized anti-GD2 MoAb (Hu3F8), Irinotecan, Temozolomide Sargramostim (GMCSF) a phase II "HITS" protocol against resistant HR-NB (NCT03189706). Noteworthy differences between HITS COG ANBL 1221 included higher temozolomide dosage overlap GMCSF. Methods: Patients were treated at Memorial Sloan Kettering (MSK) on Hospital Sant Joan de Déu (HJSD) per compassionate basis. Salient eligibility criteria evaluable or measurable chemoresistant disease. Prior irinotecan/temozolomide (IT) therapy was permitted. Each cycle, administered 3-5 weeks apart, comprised irinotecan 50 mg/m 2 /day intravenously (IV) plus 150 IV orally (days 1-5); 2.25 mg/kg/day IV, days 2,4,8 10, GMCSF 250 subcutaneously, 6-10. Toxicity measured by CTCAE v4.0 International Neuroblastoma Response Criteria. Objective (OR) also noted. The primary endpoint trial complete (CR) partial response (PR) after 4 cycles desirable rate 40%; type I errors 10% (undesirable=20%). Results: Of 90 heavily prior-treated patients (38 MSK evaluated trial, 52 HJSD), 8 had refractory induction chemotherapy while 82 up 6 prior relapses (median=1). 503 (median 5/patient) administered. Toxicities myelosuppression diarrhea expected IT, pain hypertension naxitamab, febrile neutropenia 4%. No other >grade unexpected toxicities occurred; treatment outpatient. Primary reached trial: INRC = 30.6%, lower boundary 20.4%. In entire cohort, best CR (26%), PR (11%), mixed (9%), stable (27%) PD (27%). OR noted 64%, soft tissue (48%) skeletal MIBG uptake (66%). BM seen 57%. occurred MYCN-amplified (25%), (100%) relapsed (61%) HR-NB; who previously received I/T (64%) (68%). dinutuximab/IT, 42% (5/12). Human anti-human antibody did not develop any patient (n=50). Conclusions: Naxitamab-based chemoimmunotherapy safe without immunogenicity. It effective all compartments even multiple relapses, MoAbs and/or IT.