Affimed N.V. announced updated clinical data from the ongoing AFM24-102 trial, evaluating the combination of AFM24 and atezolizumab in heavily pretreated non-small cell lung cancer (NSCLC) patients. The results, presented on December 17, 2024, demonstrate encouraging clinical activity and tolerability in both EGFR wild-type (EGFRwt) and EGFR mutant (EGFRmut) NSCLC populations.
The study offers a potential new treatment option for NSCLC patients who have progressed after multiple lines of therapy.
Efficacy in EGFR Mutant NSCLC
In the EGFRmut cohort, comprising 17 patients in the per-protocol set (PPS), the AFM24/atezolizumab combination achieved an overall response rate (ORR) of 24%, with one complete response (CR) and three partial responses (PRs). The disease control rate (DCR) was 71%, and tumor shrinkage was observed in 41% of patients. The median progression-free survival (PFS) was 5.6 months, and 29% of patients remained on treatment for over 10 months, indicating durable tumor control.
Results in EGFR Wild-Type NSCLC
For the EGFRwt cohort (33 patients in the PPS), the combination therapy demonstrated an ORR of 21% (one CR, five PRs, and one unconfirmed PR) and a DCR of 76%. Tumor shrinkage was observed in 48% of patients. The preliminary median PFS was 5.6 months, and 36% of patients were still receiving treatment at the time of data cutoff. Notably, among the responders, five had not previously achieved an objective response on prior checkpoint inhibitors (CPIs).
Safety and Tolerability
The AFM24 and atezolizumab combination was generally well-tolerated, with no unexpected safety signals. Infusion-related reactions (IRRs) were the most common adverse event, occurring in 54% of patients, but were manageable and typically resolved after the first infusion. Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), known side effects of atezolizumab, were reported in 21% and 16% of patients, respectively.
Exposure-Response Analysis and Dose Optimization
A post-hoc exposure-response analysis, including 44 NSCLC patients treated with 480 mg of AFM24, revealed a correlation between higher AFM24 exposure and improved outcomes. Patients with higher exposure exhibited an ORR of 46% and a PFS of 7.4 months. This analysis suggests that increasing the AFM24 dose could further enhance efficacy. Affimed plans to use a dose of 720 mg weekly in future development programs, based on successful testing in a phase 1 study with a manageable safety profile.
Expert Commentary
Dr. Andreas Harstrick, Chief Medical Officer of Affimed, stated, "We see compelling efficacy results with the AFM24/atezolizumab combination in heavily pretreated NSCLC patients, independent from the mutational status... The insights in the relation of exposure and efficacy will allow us to further improve on the efficacy and provide a clear path forward as we strive to unlock new possibilities for EGFR NSCLC patients."
About AFM24
AFM24 is a tetravalent, bispecific ICE® molecule that targets CD16A on innate immune cells and epidermal growth factor receptor (EGFR) on tumor cells. This mechanism of action promotes tumor cell killing through antibody-dependent cellular cytotoxicity and phagocytosis.
