A Phase II Study of Acimtamig (AFM13) in Patients with CD30-Positive, Relapsed, or Refractory Peripheral T-cell Lymphomas

Purpose: Patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) generally have poor prognoses and limited treatment options. This study evaluated the efficacy of a novel CD30/CD16A bispecific innate cell engager, acimtamig (AFM13), in patients with R/R PTCL. Patients and Methods: Patients included those with CD30 expression in ≥1% of tumor cells and who were R/R following ≥1 prior line of systemic therapy. Acimtamig (200 mg) was administered once weekly in 8-week cycles. The primary endpoint was the overall response rate by fluorodeoxyglucose-PET per independent review committee; secondary and exploratory endpoints included duration of response, safety, progression-free survival, and overall survival. Results: The overall response rate in 108 patients was 32.4% [95% confidence interval (CI), 23.7, 42.1] with a complete response rate of 10.2% (95% CI, 5.2, 17.5); the median duration of response was 2.3 months (95% CI, 1.9, 6.5). Patients with R/R angioimmunoblastic T-cell lymphoma exhibited the greatest number of responses [53.3% (95% CI, 34.3, 71.7)]. Responses were independent of CD30 expression level, prior brentuximab vedotin treatment, or steroid premedication. Acimtamig exhibited a tolerable safety profile; the most common treatment-related adverse events were infusion-related reactions in 27 patients (25.0%) and neutropenia in 11 patients (10.2%). No cases of cytokine release syndrome or acimtamig-related deaths were reported. Despite exhibiting promising clinical activity and tolerable safety in a heavily pretreated PTCL population, the study did not meet the criteria for the primary endpoint. Conclusions: The promising clinical efficacy observed warrants further investigation, and development of acimtamig for patients with R/R CD30⁺ lymphomas continues in combination with allogeneic NK cells.