The combination of CD16A/EGFR innate cell engager, AFM24, with SNK01 autologous natural killer cells in patients with advanced solid tumors.
Authors: El-Khoueiry Anthony B. , Song Paul Y. , Rubel Jennifer , Pourang Dorna Y. , Raab Christa , Hintzen Gabriele , Emig Michael , Nava-Parada Pilar 
Published: June 2022

TPS2675 Background: Natural killer (NK) cells are a critical component of the innate immune system involved in the eradication of transformed cells via antibody-dependent cellular cytotoxicity (ADCC). For treatment of solid tumors autologous NK cell transfer represents a promising treatment strategy, with ex vivo expansion and activation enhancing the specificity and anti-tumor activity of NK cells. The efficacy of this approach may be enhanced through the addition of tumor-targeting antibodies, augmenting NK cell-mediated ADCC. Innate Cell Engagers (ICE) are bispecific antibodies that target a tumor cell-surface antigen and bind to CD16A expressed on NK cells. AFM24 is a novel ICE that targets epidermal growth factor receptor (EGFR), which is often overexpressed in solid tumors. The Phase 1 study of AFM24 monotherapy showed patients had a manageable safety profile, and SNK01 monotherapy has also shown to be well-tolerated in patients with rapidly progressive solid tumors. This study seeks to investigate AFM24 in combination with SNK01 autologous NK cells in patients with advanced EGFR+ solid tumors. Methods: An ongoing Phase 1/2a open-label, non-randomized, multicenter, dose escalation (Phase 1) and dose expansion (Phase 2a) study was initiated in November 2021 (NCT05099549) to evaluate the safety, tolerability and efficacy of AFM24 in combination with SNK01 NK cells in EGFR+ solid tumors. The primary aim of the Phase 1 study is to determine the maximum tolerated dose and/or recommended Phase 2 dose (RP2D) of AFM24 in combination with SNK01 at a fixed dose NK cells using a standard 3+3 design. Eligible patients must have advanced or metastatic disease with positive immunohistochemical staining for EGFR in >1% of tumor cells and be refractory to standard-of-care treatment. Treatment begins with a safety lead-in phase with a single dose of AFM24 7 days prior to combination therapy. AFM24 will be administered at an escalating dose as weekly intravenous (IV) infusions; the starting dose (160 mg) and dose escalations for each cohort are based on results from the ongoing AFM24 monotherapy trial (NCT04259450). SNK01 NK cells will be given at a fixed dose (4.0 x109 cells) as a weekly IV infusion concomitantly with AFM24. Patients will receive combination therapy until disease progression, intolerable toxicity, patient withdrawal or termination at the investigator’s discretion. Phase 2 will then establish the overall response rate (as per RECIST v1.1) of combination therapy in patients with treatment refractory, advanced or metastatic squamous cell carcinoma of the head and neck, non-small cell lung cancer, or colorectal cancer as the primary endpoint. Efficacy will also be assessed by assessing progression-free and overall survival. Secondary endpoints for both phases include treatment-emergent adverse events, serious adverse events, pharmacokinetics and immunogenicity. Clinical trial information: NCT05099549.