3098 Background: 68Ga-AKY-2519 is a miniprotein radioconjugate developed by Aktis Oncology that targets B7-H3 (CD276) which is overexpressed in several malignancies and is linked with aggressive histology and poor outcomes. AKY-2519 is a high-affinity binder to B7-H3 that internalizes into tumor cells upon binding and thereby maximizes tumor retention. AKY-2519 is also designed to clear rapidly through the kidneys to minimize exposure to normal tissues. To identify potential utility for clinical development of 225Ac-AKY-2519 across various tumor types, here we report the first-in-human evaluation of 68Ga-AKY-2519 using positron emission tomography (PET) in patients with solid tumors. Methods: In this prospective, observational study, 18 patients with advanced solid tumors, including prostate cancer (n=7), colorectal cancer (n=4), SCLC (n=3) and NSCLC (n=1) underwent PET/CT imaging following intravenous administration of 68Ga-AKY-2519. Safety, normal tissue distribution and tumor uptake were assessed. Imaging findings were correlated with known disease sites in PSMA and FDG reference PET/CTs as well as available clinical and pathological data. Results: 68Ga-AKY-2519 was well tolerated with no adverse events. PET/CT imaging demonstrated favorable tumor uptake, rapid blood pool clearance and low uptake in normal tissues. 68Ga-AKY-2519 uptake (SUVmax) in normal tissues at 120 min post injection (p.i.) was noted in the liver (median 22.9 interquartile range (IQR) [20.9-30.8), spleen (7.3 6.4-11.4), salivary glands (7.3 6.4-11.4), adrenal glands (17.5 15.9-19.8) and kidneys (7.3 6.4-11.4). No significant bone marrow uptake was noted (median SUVmax 4.1 3.3-5.1 at 120 min p.i.). High and consistent tumor uptake was observed across various tumor types. The largest cohort was patients with metastatic prostate cancer (n=7), in which the highest 68Ga-AKY-2519 uptake was in bone metastases (median SUVmax 40.4 (120 min p.i.), SUVpeak 25, SUVmean 16.1), followed by lymph node metastases (SUVmax 13.8 (120 min p.i.), SUVpeak 6.5, SUVmean 5.1) and visceral metastases (SUVmax 31.0 (120min p.i.), SUVpeak 22.2, SUVmean 18.7). Conclusions: 68Ga-AKY-2519 PET/CT imaging of various malignancies was safe and demonstrated high tumor-to-background uptake and cancerous lesion detection at 120 min p.i. Normal tissue uptake was low, and robust tumor uptake was noted in patients across different solid tumors indicating therapeutic potential. These data warrant further clinical development of 225Ac-AKY-2519.
Enste et al. (Wed,) studied this question.