HITS Combo Meets Primary End Point for ORR in High-Risk Neuroblastoma

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Partner | Cancer Centers | <b>Memorial Sloan Kettering Cancer Center </b>

The combination of the humanized anti-GD2 antibody naxitamab-gqgk, irinotecan, temozolomide, and sargramostim met its primary end point for objective response rate in patients with chemoresistant high-risk neuroblastoma.

The combination of the humanized anti-GD2 antibody naxitamab-gqgk (Danyelza), irinotecan, temozolomide, and sargramostim (Leukine; HITS) met its primary end point for objective response rate (ORR) in patients with chemoresistant high-risk neuroblastoma (HR-NB), according results from a phase 2 trial (NCT03189706).1

The ORR was 64% with a complete response (CR) rate of 26% and a partial response (PR) rate of 11%, exceeding the prespecified primary end point of a 30.6% ORR according to the International Neuroblastoma Response Criteria. The lower boundary was 20.4%.

Naxitamab is a GD2-directed monoclonal antibody, which is highly expressed in various neuroectoderm-derived tumors and sarcomas. Shakeel Modak, MD, chief of the neuroblastoma service at Memorial Sloan Kettering Cancer Center (MSK), is scheduled to deliver the full results at the 2022 ASCO Annual Meeting.

Drug maker Y-mAbs Therapeutics issued a press release containing data from 90 heavily treated patients treated with the HITS regimen at MSK (n = 38) and Hospital Sant Joan de Déu (n = 52) in Barcelona, Spain. Eight patients were refractory to induction chemotherapy and 82 had up to 6 prior relapses.

Investigators administered cycles of treatment 3 to 5 weeks apart. The treatment regimen included 50 mg/m2 ofdaily irinotecan plus 150 mg/m2 of daily temozolomide on days 1 to 5, 2.25 mg/kg of naxitamab daily on days 2, 4, 8, and 10; and 250 mcg/m2 of granulocyte-macrophage colony-stimulating factor (GM-CSF) daily on days 6 to 10. Response assessment was based on best response over the course of 4 cycles.

The ORR was 64% in patients who had previously received irinotecan/temozolomide and 68% for those who previously received naxitamab. The ORR was 42% in patients who previously received dinutuximab/irinotecan/temozolomide. The ORR was 100% in patients with refractory disease, 61% in patients with relapsed disease, and 25% among patients with MYCN amplification. Fifty-seven percent of patients had CR in bone marrow.

Soft tissue MIBG uptake was 48% and skeletal MIBG uptake was 66%.

Toxicity fit expected safety profiles. Investigators observed myelosuppression and diarrhea, which are common with irinotecan/temozolomide, and pain and hypertension as expected with naxitamab, as well as febrile neutropenia. There were no other grade 3 or higher unexpected toxicities observed. Investigators added that none of the 50 patients who provided samples developed human anti-human antibody.

In November 2020, the FDA granted accelerated approval to naxitamab in combination with GM-CSF for pediatric patients aged 1 year of age or older and adult patients with relapsed/refractory HR-NB in the bone or bone marrow who have demonstrated a PR, minor response, or stable disease to prior treatment.2

The agency’s decision was based on data from Study 201 (NCT03363373) and Study 12-230 (NCT01757626). For both trials, investigators observed responses in the bone, bone marrow, or both.

Among 22 patients treated in the multicenter Study 201 trial, the ORR was 68%. Thirteen patients (59%) had CR. Eighty percent of patients had a response in bone, 70% of whom had CR. Seven (78%) patients had response in bone marrow, all of which were CRs.3

Among 38 patients treated in the single-arm, single-center Study 12-230 trial, the ORR was 34% with a CR of 26% and a PR of 8%. Duration of response was 6 months or more in 23% of patients.4


  1. Y-mAbs announces naxitamab chemoimmunotherapy investigational trial for high-risk neuroblastoma meets primary endpoint. News release. Y-mAbs Therapeutics. May 26, 2022. Accessed June 2, 2022. https://bit.ly/3PZaBcE
  2. FDA Approves Y-mAbs’ DANYELZA® (naxitamab-gqgk) for the treatment of neuroblastoma. News release. Y-mAbs Therapeutics. November 25, 2020. Accessed June 2, 2022. https://bit.ly/3nVyHGl
  3. Kushner BH, Morgenstern DA, Nysom K, et al. Efficacy of naxitamab in patients with refractory/relapse (R/R) high-risk neuroblastoma (HR-NB) by bone/bone marrow (BM) evaluation, potential sites of residual disease. J Clin Oncol. 2021,39(suppl 15):10022-10022. doi:10.1200/JCO.2021.39.15_suppl.10022
  4. Danyelza. Prescribing information. Y-mAbs Therapeutics, Inc. November 2020. Accessed June 2, 2022. https://bit.ly/3NgbprQ