Affimed N.V. announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to the combination therapy of Affimed’s innate cell engager (ICE®) acimtamig and Artiva Biotherapeutics’ AlloNK® (AB101) for the treatment of relapsed or refractory Hodgkin Lymphoma (R/R HL). The combination is currently under evaluation in the ongoing LuminICE-203 multicenter, multi-cohort phase 2 trial. This regulatory milestone highlights the potential of this innovative treatment to address the unmet needs of patients with R/R HL, particularly those with double refractory disease.
Expedited Development and Review
The RMAT designation is designed to expedite the development and review of regenerative medicine therapies, including cell therapies, that aim to address serious or life-threatening conditions. It provides the same expedited review benefits as a Breakthrough Therapy Designation but is exclusively focused on regenerative medicine products. This designation allows Affimed enhanced access to FDA resources, including the potential for accelerated approval and priority review, which could significantly reduce the time required to bring the acimtamig and AlloNK® combination to patients in need.
Clinical Efficacy Data
The RMAT designation was supported by early efficacy data from cohorts 1 and 2 (12 patients) of the LuminICE-203 trial. These data demonstrated an overall response rate (ORR) of 83.3% (10/12) and a complete response rate (CRR) of 50% (6/12), with a well-managed safety profile. Updated data from all four cohorts of the run-in phase of the LuminICE-203 trial were presented at the 66th ASH Annual Meeting and Exposition on December 8, 2024, showcasing the continued promise of this therapeutic approach. According to another source, in the trial, the combination demonstrated an overall response rate of 86% and a complete response rate of 55%.
Acimtamig and AlloNK Mechanism of Action
Acimtamig (AFM13) is a first-in-class ICE® that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. It induces specific and selective killing of CD30-positive tumor cells by engaging and activating natural killer (NK) cells and macrophages. Acimtamig is designed as a tetravalent bispecific innate cell engager that acts as a bridge between innate immune cells and the tumor, creating the necessary proximity for the innate immune cells to destroy the tumor cells. AlloNK® (AB101) is Artiva Biotherapeutics’ allogeneic NK cell therapy, complementing acimtamig’s mechanism by providing a readily available source of effector cells.
LuminICE-203 Trial Design
The LuminICE-203 (AFM13-203) trial is a Phase 2 open-label, multicenter, multi-cohort study evaluating the safety and efficacy of the combination of acimtamig (AFM13) with Artiva Biotherapeutics’ allogeneic NK cell AlloNK® (AB-101) in patients with relapsed/refractory classical Hodgkin lymphoma and CD30-positive peripheral T cell lymphoma (NCT05883449). The study builds on prior research, including an investigator-sponsored study (AFM13-104) that investigated acimtamig in combination with cord blood-derived NK cells in patients with refractory/recurrent CD30-positive Hodgkin or non-Hodgkin lymphoma (NCT04074746).
Potential Beyond Hodgkin Lymphoma
Beyond Hodgkin Lymphoma, this combination shows potential applicability in other CD30-positive lymphomas, such as peripheral T-cell lymphoma (PTCL), which can be resistant to conventional therapies and has a high risk of relapse. Clinical proof-of-concept in PTCL could significantly increase the commercial potential of this combination, potentially by two to three-fold compared to the patient population with double-refractory HL.
Management Perspective
“This is an important regulatory milestone demonstrating that the FDA acknowledges the critical need for new therapies in R/R HL, in particular for double refractory HL patients where there are no approved therapies,” said Dr. Shawn M. Leland, PharmD, RPh, Chief Executive Officer of Affimed. “In addition, the RMAT designation validates the strength of our growing clinical data and the promise of our innovative treatment to bring hope to patients battling this rare and difficult-to-treat cancer.”
