AFM13 IN PATIENTS WITH CD30 POSITIVE RELAPSED OR REFRACTORY (R/R) PERIPHERAL T CELL LYMPHOMA (PTCL): RESULTS FROM THE PHASE 2 REDIRECT STUDY

Introduction: PTCLs are aggressive hematologic malignancies often with poor prognoses; there is no standard of care therapy for patients with R/R PTCL. AFM13, a tetravalent, bispecific innate cell engager, binds CD30 when expressed on PTCL cells, and CD16A on innate effector cells, augmenting the innate immune response to CD30+ tumor cells. Phase 1 clinical trials of AFM13 in patients with R/R Hodgkin lymphoma (HL) and cutaneous CD30+lymphomas showed a tolerable safety profile and clinical activity; correlative science data in a small group of AFM13-responsive patients with HL showed increased natural killer (NK) cell activity. Methods: A Phase 2 study (NCT04101331) assessed the efficacy of AFM13 in patients with select R/R PTCL subtypes, exhibiting histologically confirmed CD30+expression in ≥1% tumor cells, who had received ≥1 prior systemic therapy. The primary endpoint was to assess the overall response rate (ORR) by FDG-PET per independent review committee. Secondary endpoints included safety, complete response rate (CRR), and duration of response (DoR). Progression-free survival (PFS) and overall survival (OS) were exploratory endpoints. Patients received 200 mg AFM13 intravenously once weekly until disease progression, intolerable toxicity, consent withdrawal or termination by the investigator. Results: Patients (n = 108; age 21–93; 61% male) received AFM13 with a median (min, max) number of infusions of 9.0 (1, 116). PTCL subtypes assessed (n) were: PTCL not-otherwise-specified (PTCL-NOS, 41); angioimmunoblastic T cell lymphoma (AITL, 30); anaplastic large cell lymphoma (ALCL, 26); other (11). Patients had received a mean 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 per subtype 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. AFM13-related treatment emergent adverse events (TEAEs) occurred in 79/108 patients (73.1%); 14 events in 9 patients (8.0%) were considered serious. The most frequent TEAE was infusion-related reactions, as reported by the investigator, seen in 34/108 patients (31.5%), including 12 Grade 3 events in 6 patients (5.7%). Neutropenia was the most frequent Grade ≥3 TEAE occurring in 9.3% of patients. Conclusion: AFM13 monotherapy demonstrated robust clinical activity in heavily pretreated patients with R/R PTCL. The safety profile of AFM13 was well managed and consistent with previously reported data from prior and ongoing clinical studies with AFM13. These data support future evaluation of AFM13 in combination with other immunotherapies, including allogeneic NK cells, to further potentiate anti-tumor immune responses to CD30+ lymphomas. Keyword: immunotherapy Encore Abstract—previously submitted to AACR 2023 The research was funded by: Affimed GmbH Conflicts of interests pertinent to the abstract W. S. Kim Research funding: Sanofi; BeiGene; Boryung; Roche; Kyowa Kirin Co., Ltd.; Dong-A Pharmaceutical Co., Ltd. J. Shortt Consultant or advisory role: Bristol Myers Squibb; Novartis; Otsuka; Astellis; Mundipharma; Pfizer Research funding: Astex; Amgen; Bristol Myers Squibb; Novartis P. L. Zinzani Consultant or advisory role: MSD; Eusapharma; Novartis; Celltrion Healthcare; Gilead; Janssen-Cilag; Bristol Myers Squibb; Servier; AstraZeneca; Takeda; Roche; Kyowa Kirin; Incyte; BeiGene; Secura Bio; Sandoz; ADC Therapeutics A. Marin-Niebla Other remuneration: Janssen; Gilead-Kite; Roche; Eli Lilly; Takeda; Kiowa-Kirin; AbbVie; AstraZeneca; BeiGene K. Alexis Employment or leadership position: Affimed Inc. Stock ownership: Affimed Inc. M. Emig Employment or leadership position: Affimed GmbH Stock ownership: Affimed GmbH L. Garcia Employment or leadership position: Affimed Inc. Stock ownership: Affimed Inc. A. Overesch Employment or leadership position: Affimed GmbH Stock ownership: Affimed GmbH K. Pietzko Employment or leadership position: Affimed GmbH Stock ownership: Affimed GmbH S. Horwitz Consultant or advisory role: Affimed; Daiichi Sankyo; Kyowa Kirin; ONO Pharmaceuticals; SecuraBio; Takeda; Shoreline Pharmaceuticals; Yingli Pharma; Abcuro Inc. Tublulis GmbH Research funding: ADC Therapeutics; Auxilius Pharma; Celgene; CRISPR Therapeutics; Millennium/Takeda; Seattle Genetics; C4 Therapeutics; Verastem/SecuraBio