Preliminary results from the phase 2 study of AFM24 in combination with atezolizumab in patients with EGFR wild-type (EGFR-WT) non-small cell lung cancer (NSCLC).
Authors: Kim Hye Ryun , Saavedra Omar , Cervantes Andres , Lugowska Iwona A. , Oberoi Arjun , El-Khoueiry Anthony B. , Thomas Jacob Stephen , Rogowski Wojciech , Lopez Juanita Suzanne , Shim Byoung Yong , Christenson Eric , Boni Valentina , Garassino Marina Chiara , Yarza Ramon , Gaertner Ulrike , Lutkewitz Sarah , Shuetz Daniel , Pietzko Kerstin , Emig Michael , Morales Espinosa Daniela 
Published: June 2024

2522 Background: Immunotherapy combinations could be a promising strategy to overcome resistance to existing therapies. AFM24, a first in class, bispecific, tetravalent innate cell engager, binds CD16A on innate effector cells (NK cells and macrophages) and EGFR on solid tumors, redirecting and enhancing the innate and possibly the adaptive immune response towards tumors. Atezolizumab, a PD-L1 inhibitor, abrogates activation of the PD-1 immune checkpoint, potentiating the adaptive immune response. This Phase 1/2a study (NCT05109442) is evaluating if combining AFM24 with atezolizumab synergistically enhances both innate and adaptive immunity to effectively target EGFR+ solid tumors. Here we report initial results of the EGFR-WT NSCLC expansion cohort. Methods: The recommended Phase 2 dose of 480 mg AFM24 is given intravenously (IV) weekly in combination with 840 mg atezolizumab IV fortnightly, in patients with advanced or metastatic EGFR-WT NSCLC who progressed on ≥1 prior line of therapy including at least a platinum doublet and a checkpoint inhibitor (CPI). The primary endpoint is overall response rate by RECIST v1.1 by Investigator assessment. Secondary endpoints include safety, pharmacokinetics, and immunogenicity. Treatment is given in four-week cycles until disease progression, intolerable toxicity, investigator discretion, or patient withdrawal of consent. Tumor assessments are performed at screening, cycles 2, 4, 6, 8, 10, 12; and every three cycles thereafter. Results: As of January 2024, 17 patients in the EGFR-WT NSCLC cohort received AFM24 and atezolizumab for a mean (range) duration of 14.4 (1–33) weeks. Median (range) age is 66 (45–75) years; 82.4% male; European Cooperative Oncology Status Performance Score 0–1; median (range) number of prior lines is 2 (1–5). The combination was well tolerated with no new or unexpected toxicities observed compared to each single agent. The most common AFM24-related adverse events were infusion-related reactions (10 Grade 1–2, two Grade 3). Of the 15 response-evaluable patients, one complete response and three PRs were confirmed; two showed shrinkage of ≥50% in target lesions from baseline. All responders were resistant to prior CPI. Seven patients achieved stable disease as BOR. After a median follow-up time of 5.5 (95% CI 3.45; 5.55) months, 8 patients are still on treatment including all responders. Conclusions: AFM24 with atezolizumab shows remarkable signs of clinical efficacy, even in patients with resistance to prior CPI, and a well-tolerated and manageable safety profile in patients with EGFR-WT NSCLC. The study is ongoing and up to 40 patients will be enrolled into this cohort. Clinical trial information: NCT05109442 .