Background
Phase II, open-label, single-arm study. 108 patients with CD30-positive R/R PTCL (including ALCL, AITL, PTCL-NOS, and other subtypes) after ≥1 prior line including brentuximab vedotin. AFM13 (acimtamig) is a tetravalent bispecific innate cell engager (ANKET) targeting CD30 (on tumor) and CD16A (on NK cells and macrophages), engaging innate immunity without T-cell dependency, mechanistically distinct from conventional T-cell-engaging bispecifics.
Interventions and follow up
Regimen: AFM13 (acimtamig) 200 mg IV weekly + cord blood–derived AlloNK (CD16/IL-15–engineered allogeneic NK cells) infusion after fludarabine/cyclophosphamide lymphodepletion in R/R CD30+ lymphomas
Primary endpoint: Overall response rate (independent review committee)
Median follow up: 8.2 months
Primary endpoint: Overall response rate (independent review committee)
Median follow up: 8.2 months
Results
ORR (primary): 32.4% (95% CI 23.8–42.1%)
CR rate: 10.2%
Median DoR: 4.5 months
Median PFS: 2.8 months
Subgroup — AITL: ORR 53.3% (highest response rate of any subtype)
Subgroup — sALCL (post-BV): ORR 38.1%
CR rate: 10.2%
Median DoR: 4.5 months
Median PFS: 2.8 months
Subgroup — AITL: ORR 53.3% (highest response rate of any subtype)
Subgroup — sALCL (post-BV): ORR 38.1%
Adverse events
Immune/infusion: Infusion-related reactions any grade 39.8% (grade ≥3 2.8%); no CRS or ICANS observed
Hematologic/overall: Grade ≥3 AEs 42.6%; grade ≥3 neutropenia 11.1%; grade ≥3 fatigue 4.6%; treatment discontinuation due to AEs 3.7%
Hematologic/overall: Grade ≥3 AEs 42.6%; grade ≥3 neutropenia 11.1%; grade ≥3 fatigue 4.6%; treatment discontinuation due to AEs 3.7%
Conclusions
Acimtamig demonstrated a 32.4% ORR in heavily pretreated CD30+ R/R PTCL, with the highest activity in AITL (53.3%), and a favorable tolerability profile notable for absence of CRS/ICANS. The innate cell engagement mechanism provides a distinct approach for patients who have exhausted T-cell–directed therapies.
Key Limitations
Single-arm phase II with short follow-up (8.2 months); responses were generally not durable (median DoR 4.5 months, median PFS 2.8 months). Overall ORR was modest (32.4%) with activity concentrated in the AITL subgroup. The AlloNK combination adds logistical complexity (lymphodepletion, allogeneic cell product). No randomized comparator; durability and survival benefit remain unproven.
Clinical Context
AFM13 + AlloNK is investigational and not FDA/EMA approved. For R/R CD30+ PTCL, established options per ASCO/ESMO include brentuximab vedotin (for ALCL) and single-agent regimens (pralatrexate, romidepsin, belinostat) bridging to allogeneic transplant where feasible. Innate cell engager strategies remain in early development and are not yet incorporated into guideline-recommended pathways.