NB02 (Poseltinib) combined rituximab and lenalidomide in R/ R PCNSL (POTENTIAL-P): Initial results of safety lead-in cohort.

Abstract

Abstract Background: Primary central nervous system lymphoma (PCNSL) is a rare, highly aggressive B-cell non-Hodgkin lymphoma confined to the central nervous system, and it is associated with poor prognosis. Despite initial treatment, a substantial number of patients have relapsed or refractory (R/R) disease, and there is no established standard of care for R/R PCNSL. NB02 (poseltinib) is a safe and potent selective Bruton's tyrosine kinase (BTK)/Tec protein tyrosine kinase (TEC) inhibitor with high CNS penetration profile. Previous studies have shown promising efficacy and favorable safety for poseltinib in combination with lenalidomide and anti-CD20 antibodies in large B-cell lymphomas. Based on these observations, we expect the combination of poseltinib, lenalidomide and rituximab will yield promising results in patients with R/R PCNSL. Study design and Methods: This multi-center, single-arm, phase II study will enroll 33 patients with R/R PCNSL from 15 sites in South Korea (NCT06737250). Key inclusion criteria include adults (19-80 years), an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2, pathologically confirmed CD20-positive PCNSL, and disease that is relapsed or refractory after one or two prior lines of systemic therapy. Key exclusion criteria include prior treatment with a BTK inhibitor and known refractoriness to lenalidomide. The regimen consists of six induction cycles followed by a maintenance phase. During induction, patients receive poseltinib 60 mg BID (days 1-21), lenalidomide 20 mg QD (days 1-14), and rituximab 375 mg/m² IV on day 1 (Days 1, 8 and 15 in Cycle 1) every 21 days. During maintenance, patients receive poseltinib and lenalidomide. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The first six patients will constitute a safety lead-in cohort. Results: As of the data cutoff date (July 23, 2025), six patients have been enrolled in the safety lead-in cohort. The median age was 59 years (range, 50-73), and three patients (50%) were female. All patients had received prior systemic therapy based on high-dose methotrexate +/- rituximab. Two patients had received radiation therapy, and two had undergone autologous stem cell transplantation. The combination regimen was generally well-tolerated, no dose-limiting toxicities (DLTs) were observed in evaluation period. Grade 3-4 adverse events (AEs) occurred in two of the six patients, and included neutropenia (n=2), thrombocytopenia (n=1) and elevated AST/ALT (n=1). Grade 1-2 AEs, skin-related AEs (n=3) and abdominal pain (n=1), were reported in three patients. No treatment discontinuations due to adverse events occurred. Of the first two patients evaluable for response, both achieved an objective response (1 complete response and 1 partial response). The patient with partial response experienced disease progression at 3 months. The remaining four patients had not yet undergone their first disease evaluation. At the data cutoff, five patients remained on treatment, three of whom had received more than three cycles of therapy. Conclusion: These initial results from the safety lead-in cohort suggest that the combination of poseltinib, rituximab, and lenalidomide has a manageable safety profile and demonstrates promising preliminary anti-tumor activity in patients with R/R PCNSL. Enrollment in the study is ongoing, and updated results will be presented.