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First-in-Human Phase I Study of a CD16A Bispecific Innate Cell Engager, AFM24, Targeting EGFR-Expressing Solid Tumors
Anthony El-Khoueiry1, Omar Saavedra2,3, Jacob Thomas1
1Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Summary
AFM24, a novel bispecific innate cell engager, shows promise for treating EGFR-expressing solid tumors. This therapy was well-tolerated, with 480 mg identified as the recommended phase II dose for further development.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Innate immune cell-based therapies demonstrate significant antitumor potential in various cancers.
- AFM24 is a bispecific innate cell engager designed to target CD16A on immune cells and EGFR on tumor cells, thereby directing immune responses against tumors.
Purpose of the Study:
- To evaluate the safety and tolerability of AFM24 in a phase I/IIa dose-escalation/dose-expansion study.
- To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of AFM24.
- To assess pharmacokinetic properties and preliminary antitumor activity of AFM24.
Main Methods:
- A phase I/IIa dose-escalation study involving 35 patients with advanced, recurrent, or persistent EGFR-expressing solid tumors.
- AFM24 was administered weekly across seven dose cohorts (14-720 mg).
- Dose-limiting toxicities, treatment-emergent adverse events, pharmacokinetics, and tumor immune response were evaluated.
Main Results:
- AFM24 was generally well-tolerated, with infusion-related reactions being the most common dose-limiting toxicity, manageable with premedication.
- The recommended phase II dose (RP2D) was established at 480 mg.
- Pharmacokinetics demonstrated dose proportionality, and CD16A receptor occupancy on NK cells approached saturation at 320-480 mg. Stable disease was observed in 10/35 patients.
Conclusions:
- AFM24 exhibits a favorable safety profile and suitable pharmacokinetic properties for further clinical development.
- The recommended phase II dose of 480 mg supports its potential as a novel therapy for EGFR-expressing solid tumors.
- AFM24 demonstrated the ability to activate innate and adaptive immune responses within tumors, suggesting potential for combination therapies.
