Naxitamab (NAX) is a humanized GD2-binding monoclonal antibody approved in the US with granulocyte-macrophage colony-stimulating factor (GM-CSF) under accelerated approval based in part on ad hoc analysis of data from the registrational phase II 201 trial (NCT03363373). We report progression free (PFS) and overall survival (OS) results of prespecified interim analyses.
This ongoing trial is evaluating NAX+GM-CSF in patients (pts) with relapsed/refractory high-risk neuroblastoma with residual disease in bone/bone marrow (BM). Pts with progressive or residual soft tissue disease were excluded. NAX was given intravenously on days 1/3/5 at 3mg/kg/day with GM-CSF subcutaneously on days -4 to 5; cycles repeated every 4 weeks (wks). Efficacy was evaluated centrally by independent pathology and radiology review per International Neuroblastoma Response Criteria (Park et al 2017). Kaplan-Meier (KM) analysis estimated duration of response (DoR), OS and PFS.
At data cutoff (Dec 31, 2021), 52 pts with evaluable disease at baseline were eligible for efficacy assessment. Analyses showed 50% overall response rate (ORR; [95% CI 36-64%], 30% complete response (CR) rate [95% CI 25-53%] and 12 partial response (PR) rate [95% CI 4-23%]. Median number of cycles to onset of response in pts with CR or PR (n=26) was 2 (range 2-4), the same for pts with CR only (n=20) (range 2-8). Median number of wks to CR or PR was 6.7 (range 5.4-30.7). Median DoR was not estimable (NE; [95% CI, 24.9-NE]), i.e., 20 of 26 responders had ongoing response. See table for OS and PFS results. Frequent CTCAE grade 3 adverse events (AEs; safety population n=74) included hypotension (58%) and pain (54%); 6.8% of pts discontinued NAX due to AEs. Table: 62MO
|KM estimates||PFS (N=52)||OS (N=52)|
|Median wks [95% CI]||30.3 [18.4 – NE]||NE* [140 – NE]|
|At 26 wks [95%CI]||59.8% [43.8 – 72.7]||95.7% [84, 98.9]|
|At 52 wks [95% CI]||34.9% [17.3 – 53.2]||93.2 [80.3, 97.8]|
NAX+GM-CSF provided durable and clinically significant ORR and CR, and promising OS and PFS. With a manageable safety profile and an option for outpatient administration NAX treatment addresses a significant unmet medical need.
Clinical trial identification
Legal entity responsible for the study
J. Mora: Financial Interests, Personal, Advisory Role: Y-mabs. D.A. Morgenstern: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Clarity Pharmaceuticals, EUSA Pharma, Roche, Y-mabs Therapeutics, Oncoheroes Biosciences. K. Nysom: Financial Interests, Personal, Advisory Role: Y-mAbs, EUSA Pharma, Bayer; Financial Interests, Personal, Invited Speaker: Y-mAbs, Bayer; Financial Interests, Personal, Other, Data Monitoring Committee: Lilly. J. Faber: Financial Interests, Institutional, Invited Speaker: Y-mAbs Therapeutics Inc.; Non-Financial Interests, Personal, Principal Investigator: Y-mAbs Therapeutics Inc.; Non-Financial Interests, Institutional, Other, Participation in compassionate use program: Y-mAbs Therapeutics Inc. M. Bear: Financial Interests, Personal, Advisory Role: Y-mAbs. K. Tornøe: Financial Interests, Personal, Full or part-time Employment: Y-mAbs; Financial Interests, Personal, Stocks/Shares: Y-mAbs. P.S. Sørensen: Financial Interests, Personal, Full or part-time Employment: Y-mAbs; Financial Interests, Personal, Stocks/Shares: Y-mAbs. All other authors have declared no conflicts of interest.