Abstract 754P
Background
AFM24 is an EGFR/CD16A bispecific innate cell engager binding to natural killer (NK) cells and macrophages, inducing potent antibody mediated cytotoxicity and phagocytosis of tumor cells in vitro.
Methods
This phase 1 study evaluated the safety, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) of AFM24 in patients (pts) with metastatic, treatment refractory solid tumors known to express EGFR. AFM24 was given intravenously QW at 14–720 mg in 28-day cycles until disease progression, intolerable toxicity, investigator’s discretion, or patient withdrawal.
Results
As of March 2022, 34 pts were treated with AFM24; median (range) age 58 (29–81) years; prior therapies 4 (2–11); total AFM24 doses given 8 (1–29). Tumor types included mainly colorectal (18/34; 12 KRAS mutant) and non-small cell lung cancer (8/34; 7 EGFR mutant). AFM24-related treatment-emergent adverse events (TEAEs) included infusion-related reactions (IRR, 25/34), nausea (8/34), and acneiform dermatitis (7/34). Seven pts had AFM24-related, transient, reversible G3–4 TEAEs (2 G3 IRRs, 1 G3 hypertension, 1 G3 dermatitis acneiform, 4 ≥G3 lymphocytopenia); there were no on-study deaths. One dose-limiting toxicity occurred at 40 mg (G3 IRR). The maximum tolerated dose has not been reached. Stable disease (SD) was observed in 10/27 evaluable pts; 4 pts had SD for ≥4 months. Dose proportional increase in PK was observed at doses ≥320 mg. CD16A receptor occupancy on circulating blood cells was dose-dependent and appeared to level off between 320–480 mg. Comprehensive PD studies of cytokines (including TNFα, IFNγ) and immune cells in peripheral blood and tumor biopsies indicated activation of the innate as well as the adaptive immune system starting at 160 mg. From these findings, the recommended phase 2 dose was determined at 480 mg. Treatment is ongoing in 4 pts (final data at ESMO).
Conclusions
AFM24 was well-tolerated and enrollment into disease specific cohorts at 480 mg has begun. Early biomarker data demonstrate target engagement with expected immune activation. Studies are also evaluating AFM24 in combination with atezolizumab, or with autologous NK cells exploring its potential to activate the innate immune response.
Clinical trial identification
NCT04259450.
Editorial acknowledgement
Editorial assistance was provided by Meridian HealthComms Ltd.
Legal entity responsible for the study
Affimed GmbH.
Funding
Affimed GmbH.
Disclosure
B. Rehbein: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH. G. Hintzen: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH. K. Pietzko: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH. C. Raab: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH. E. Rajkovic: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH. P. Ravenstijn: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH. D. Rivas: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH. M. Emig: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH. All other authors have declared no conflicts of interest.