Work

S219: First Clinical Study of the Anti-signal Regulatory Protein-alpha (sirpα) Antibody Cc-95251 Combined With Rituximab in Patients With Relapsed/refractory (r/r) Non-hodgkin Lymphoma (nhl)

Year: 2022

Type: article

Abstract: Background: CD47 is a cell-surface ligand overexpressed in various malignancies that binds to SIRPα on effector macrophages to promote tumor cell evasion of phagocytosis. Blockade of this CD47–SIRPα interaction enhances phagocytosis mediated by tumor-targeting antibodies, such as rituximab (ritux). Agents targeting CD47 combined with ritux have demonstrated promising clinical activity in R/R NHL; however, the broad expression of CD47 potentially acts as an antigen sink, reducing anti-tumor activity, and leads to on-target, off-tumor toxicities, including hemolytic anemia. CC-95251 is a novel, fully human immunoglobulin G1 antibody (Ab) that binds to SIRPα on macrophages to potently block the CD47–SIRPα interaction. Aims: The primary objectives of this multicenter, open-label, phase 1, dose-escalation and dose-expansion study were to evaluate the safety and tolerability of escalating doses of CC-95251 + ritux and to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose for the combination in patients (pts) with CD20+ R/R NHL (NCT03783403). Here, we report interim results. Methods: Pts were treated in 28-day cycles (C) with CC-95251 administered intravenously at doses of 3, 10, or 20 mg/kg every week (QW) and with ritux 375 mg/m2 on days (D) 1, 8, 15, and 22 of C1, D1 of C2–5, and D1 of every other cycle C6–24 until disease progression or unacceptable toxicity. Results: As of 5 August 2021, 17 pts had received ≥ 1 dose of CC-95251 + ritux. Median age was 67 (range 30–84) years. Pts had received a median of 3 (range 1–7) prior systemic therapies, with 100% of pts having a prior history of anti-CD20 Ab exposure. Enrolled tumor types included R/R diffuse large B-cell lymphoma in 13 (77%) pts, follicular lymphoma in 2 (12%), and mantle cell lymphoma and marginal zone lymphoma in 1 (6%) pt each. Twelve (71%) pts had disease refractory to any prior line of therapy (LOT), including 10 (59%) refractory to any anti-CD20 Ab-containing regimen, and 9 (53%) to their last LOT. Pts received a median of 4 (range 1–14) cycles of CC-95251. Median duration of treatment was 16.4 (range 2.1–53.1) weeks. There was 1 CC-95251 dose reduction, and 6 (35%) pts experienced ≥ 1 treatment-emergent adverse event (TEAE) leading to CC-95251 dose interruption. MTD has not been reached. Neutropenia and infection were the most common TEAEs for any grade (71% and 59% respectively) and grade ≥ 3 (59% and 29% respectively). Treatment-related adverse events of grade ≥ 3 included neutropenia in 9 pts (53%) and infection in 2 pts (12%); no treatment-related anemia or deaths were reported. Overall response rate in the efficacy evaluable population was 56% (9/16), with 4 (25%) pts achieving a complete response (CR). Of 9 pts refractory to any prior anti-CD20 Ab-containing regimen, 2 pts achieved a CR and 2 pts had stable disease. Median time to response was 7.9 weeks. Duration of response ranged 7.4–28.1 weeks with a CR ongoing in 1 pt. In this dose-escalation study, CC-95251 demonstrated dose-proportional increases in exposure at doses > 3 mg/kg QW and full receptor occupancy at doses ≥ 3 mg/kg. Summary/Conclusion: CC-95251 + ritux demonstrated a manageable safety profile and promising efficacy in pts with heavily pretreated CD20+ R/R NHL. The study is currently enrolling in the dose-expansion phase.

Source: HemaSphere

DOI: 10.1097/01.hs9.0000843768.58631.ac