First-in-Human Phase 1 study of a CD16A bispecific innate cell engager, AFM24, targeting EGFR-expressing solid tumors.

Abstract

Purpose: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on natural killer (NK) cells/macrophages and EGFR on tumor cells, redirecting antitumor activity towards tumors. The safety and tolerability of AFM24 was evaluated in this Phase 1/2a dose escalation/dose expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

Methods: The main objective in Phase 1 was to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). The primary endpoint was the incidence of dose-limiting toxicities (DLTs) during the observation period. Secondary endpoints included the incidence of treatment emergent adverse events and pharmacokinetics.

Results: In the dose escalation phase, 35 patients received AFM24 weekly across seven dose cohorts (14-720 mg). One patient experienced a DLT of Grade 3 infusion-related reaction (IRR). IRRs were mainly reported after the first infusion; these were manageable with premedication and a gradual increase in infusion rate. Pharmacokinetics were dose-proportional and CD16A receptor occupancy on NK cells approached saturation between 320-480 mg. Paired tumor biopsies demonstrated activation of innate and adaptive immune responses within the tumor. Best objective response was stable disease in 10/35 patients; four had stable disease for 4.3-7.1 months.

Conclusions: AFM24 was well tolerated with 480 mg established as the RP2D. AFM24 could be a novel therapy for patients with EGFR-expressing solid tumors with suitable tolerability and appropriate pharmacokinetic properties for further development in combination with other immuno-oncology therapeutics.