Abstract CT024: REDIRECT: A Phase 2 study of AFM13 in patients with CD30-positive relapsed or refractory (R/R) peripheral T cell lymphoma (PTCL)
Authors: Kim Won Seog , Shortt Jake , Zinzani Pier Luigi , Mikhaylova Natalya , Marin-Niebla Ana , Radeski Dejan , Ribrag Vincent , Domenech Eva Domingo , Sawas Ahmed , Alexis Karenza , Emig Michael , Garcia Linta , Overesch Andre , Pietzko Kerstin , Horwitz Steven 
Published: April 2023

PTCLs are aggressive hematologic malignancies often with poor prognoses; for patients with R/R PTCL there is no standard-of-care therapy and novel treatments are required. AFM13 is a tetravalent, bispecific Innate Cell Engager (ICE ® ) that binds CD30 when expressed on PTCL cells, and CD16A on innate effector cells, redirecting and enhancing the innate immune response to CD30+ tumor cells. Phase 1 clinical studies of AFM13 in patients with R/R Hodgkin lymphoma and cutaneous CD30+ lymphomas showed a tolerable safety profile and clinical activity; early correlative science data in a small group of patients with HL showed increased natural killer (NK) cell activity in responsive patients. A Phase 2, open-label, multi-cohort study (NCT04101331) assessing the efficacy of AFM13 in patients with R/R PTCL was initiated in 2019. Patients had histologically confirmed CD30 expression in ≥1% of tumor cells and had received ≥1 prior systemic therapy. The primary endpoint was to assess the overall response rate (ORR) based on FDG-PET per independent review committee. Secondary endpoints included safety, complete response rate (CRR), duration of response (DoR), pharmacokinetics, immunogenicity, and quality of life. Progression-free survival (PFS) and overall survival (OS) were exploratory endpoints. Patients received 200 mg AFM13 intravenously once weekly until disease progression, intolerable toxicity, termination at the investigator’s discretion, or withdrawal of consent. A total of 108 patients (age 21-93; 61% male) received AFM13, with a median (min, max) number of infusions of 9.0 (1, 116). Numbers of patients per PTCL subtype assessed were: PTCL not-otherwise-specified (PTCL-NOS), 41; angioimmunoblastic T cell lymphoma (AITL), 30; anaplastic large cell lymphoma (ALCL), 26; other, 11. Patients received a mean number of 2.7 prior treatment lines; 46.3% received prior brentuximab vedotin (BV), 17.6% received prior auto-transplant. The ORR was 32.4% (CRR was 10.2%); ORR in each subgroup was 22.0% (PTCL-NOS), 53.3% (AITL), 23.1% (ALCL), and 36.4% (other). Median DoR, PFS, and OS were 2.3 months, 3.5 months, and 13.8 months, respectively. Reported treatment emergent adverse events (TEAEs) were as anticipated based on previous studies. AFM13-related TEAEs occurred in 79/108 patients (73.1%), with 14 events in 9 patients (8%) considered serious. The most frequent TEAE was infusion-related reactions, observed in 34/108 patients (31.5%), including 12 Grade 3 events in 6 patients (5.7%). Neutropenia was the most frequent TEAE with Grade ≥3 occurring in 9.3% of patients. AFM13 monotherapy was well managed and showed robust clinical activity in selected R/R PTCL subtypes. These data, together with encouraging preliminary efficacy seen in AFM13 combination studies in HL, support further evaluation of AFM13 in combination with NK cells to augment the innate immune response to CD30+ tumors.

Citation Format: Won Seog Kim, Jake Shortt, Pier Luigi Zinzani, Natalya Mikhaylova, Ana Marin-Niebla, Dejan Radeski, Vincent Ribrag, Eva Domingo Domenech, Ahmed Sawas, Karenza Alexis, Michael Emig, Linta Garcia, Andre Overesch, Kerstin Pietzko, Steven Horwitz. REDIRECT: A Phase 2 study of AFM13 in patients with CD30-positive relapsed or refractory (R/R) peripheral T cell lymphoma (PTCL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT024.