Clinical trial in progress: BCC022 a phase II trial of tipifarnib and naxitamab for relapsed/refractory neuroblastoma

Background: Tipifarnib is an oral agent that has been investigated for the treatment of hematologic malignancies and solid tumors in both adult and pediatric patients as monotherapy or in combination. Tipifarnib inhibits farnesyltransferase which is crucial for the function of certain proteins, including HRAS, which is often involved in cancer development and maintenance. By blocking this enzyme, Tipifarnib can help prevent cancer cells from multiplying and spreading. In pre-clinical work, Tipifarnib in combination with anti-GD2 immunotherapy restores the NK cell anti-tumor activity, at least in part by blocking the secretion of small extracellular vesicles from neuroblastoma (NB) cells. This combination results in a unique mechanism to restore sensitivity to immunotherapy for the treatment of relapsed/refractory (r/r) NB, and has the potential to greatly impact the outcomes with patients with r/r NB. Methods: Tipifarnib is used in an open label, multicenter, Phase II study (NCT06540963) in combination with naxitamab for subjects with r/r NB. Subjects receive six 28-day cycles with oral tipifarnib twice daily (days 1-7 and 15-21) combined with intravenous naxitamab on Days 1, 3, and 5 of each cycle. The primary objective is to evaluate the activity based on overall response rate (ORR) with secondary objectives evaluating event free survival (EFS), overall survival (OS), and duration of response (DOR). The trial will enroll pathologically confirmed NB subjects with r/r disease following standard multiagent induction therapy in two cohorts: (1) patients with disease limited to bone and/or bone marrow at enrollment. Subjects must have primary refractory disease or an incomplete response to salvage treatment after relapse or progression. In all cases, subjects must have stable disease, minor response, or partial response to their most recent therapy; (2) all other high-risk r/r NB patients not eligible for Cohort 1, including subjects with soft tissue disease. Eligibility criteria include age ≤21 years at initial diagnosis and >12 months at enrollment (first six subjects restricted to ≥6 years), and disease staging within four weeks prior to treatment. A projected 90 evaluable subjects (70 in cohort 1 and 20 in cohort 2) will be enrolled at up to 30 Beat Childhood Cancer Research Consortium hospitals. As of January 2026, enrollment is ongoing at 9 hospitals, with approximately 3% of the planned population enrolled.