AFM13 IN PATIENTS WITH R/R PERIPHERAL T CELL LYMPHOMA (PTCL): A POST-HOC SUBGROUP ANALYSIS FROM THE REDIRECT STUDY.

Abstract

Background: PTCLs are a group of aggressive hematologic malignancies with generally poor prognoses. No standard-of-care therapy is established for patients with relapsed or refractory (R/R) PTCL and novel treatments are required. AFM13, a tetravalent, bispecific Innate Cell Engager (ICE), has shown a well-managed safety profile and promising clinical efficacy in Phase 1 studies involving patients with R/R Hodgkin lymphoma (HL) and cutaneous CD30-positive (CD30+) lymphomas. ICE act by binding CD30 when expressed on tumor cells, and CD16A on natural killer (NK) cells, redirecting and potentiating NK cell mediated lysis of tumor cells. Early correlative science data in a small group of patients with HL showed increased NK cell activity in responsive patients. AFM13 may provide an effective treatment approach for patients with CD30+ PTCL. Aim(s): To perform an additional post-hoc analysis of AFM13 efficacy based on a comprehensive list of characteristics; subgroups where meaningful differences in AFM13 response were observed are presented here. Method(s): A Phase 2 study (NCT04101331) recently assessed the efficacy of AFM13 in patients with histologically confirmed CD30+ R/R PTCL, having received >=1 prior line of systemic therapy. Patients received 200 mg AFM13 intravenously once weekly until disease progression, intolerable toxicity, withdrawal of consent, or termination at the investigator's discretion. The primary endpoint was assessment of the overall response rate (ORR) by FDG-PET per independent review committee. Result(s): A total of 108 patients (age 21-93; 61% male; mean prior lines was 2.7, [46.3% with brentuximab vedotin]) were enrolled; PTCL subtypes assessed were PTCL not-otherwise-specified, angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma, other. AFM13 showed a well-managed safety profile, with AFM13 related treatment-emergent adverse events (AEs) occurring in 79/108 patients (73.1%), with 14 events in 9 patients (8%) considered serious. The most common AE was infusion-related reactions reported in 34 patients, with 12 events in 6 patients considered Grade 3, and 9 serious events in 5 patients observed. The median duration of response, progression-free survival, and overall survival were 2.3, 3.5, and 13.8 months, respectively. The ORR and complete response rate in each PTCL subtype is stated in Table 1; AITL showed the highest response rate. The ORR was considered meaningfully different in the following subgroups: lymphocytes at baseline, C-reactive protein (CRP) at baseline and sex. Patients with >0.9x109 lymphocytes/L at baseline exhibited a greater response rate (43.8%) compared to patients with <=0.9x109/L (23.3%). Conversely, patients with relatively low CRP at baseline (<=179.8 nmol/L) had a higher response rate (41.1%) than patients with CRP levels above this threshold (23.1%). Female patients (n=42) demonstrated a higher response rate than male patients (n=66), with response rates of 42.9% and 25.8%, respectively. No meaningful difference in ORR was found in subgroups based on number of prior lines and steroid premedication. Summary/Conclusion: AFM13 continues to show robust single agent activity and a well-managed safety profile in patients with PTCL refractory to standard therapy. The ORR is comparable to therapies approved for this indication, and subgroup analysis from this study suggests potential patient characteristics which may predict a more favorable response to AFM13. These data support further clinical development of AFM13, including in combination with allogeneic NK cells, to augment the innate immune response to CD30+ tumors.