The U.S. Food and Drug Administration (FDA) has granted fast track designation to [68Ga]Ga‑DPI‑4452 (ITM‑94), a diagnostic radiopharmaceutical intended for detecting clear cell renal cell carcinoma (RCC), according to ITM Isotope Technologies Munich SE.
ITM‑94 targets carbonic anhydrase IX (CAIX), a cell-surface protein frequently overexpressed in clear cell RCC. The compound serves as the diagnostic component of a theranostic pair with [177Lu]Lu‑DPI‑4452 (ITM‑91), now in clinical testing as a therapeutic radioligand.
Early Clinical Data Demonstrate Tumor‑Specific Uptake
Preliminary findings from the ongoing first‑in‑human phase 1/2 study (NCT05706129) showed high tumor‑to‑background uptake and favorable tolerability in patients with histologically confirmed clear cell RCC. In three patients (ages 48, 51, and 54 years), mean administered activity ranged from 174 to 198 MBq. Tumor‑specific uptake was evident within 15 minutes of injection and remained stable up to four hours.
Across 36 lesions, the maximum standardized uptake value (SUVmax) ranged from 6.8 to 211.6 (mean, 64.6). Metastases in bone, lymph nodes, lungs, pancreas, and parotid glands were visualized that were not clearly detected with conventional CT or MRI. The low renal parenchymal background signal facilitated precise tumor identification.
Safety and Dosimetry
ITM‑94 demonstrated a favorable safety profile with no clinically relevant toxicities. Reported treatment-emergent adverse events—headache and elevated blood creatine kinase—were mild and unrelated to the tracer. No significant changes were observed in laboratory parameters or vital signs.
Absorbed doses were lowest in the kidney, liver, and bone marrow. The small intestine (0.30 mGy/MBq) and stomach wall (0.33 mGy/MBq) showed the highest mean absorbed doses, while the mean whole‑body effective dose was 0.06 mSv/MBq. More than 80% of injected activity cleared from the bloodstream within one hour, with urinary excretion accounting for up to 13% of the injected dose.
Continued Development of the ITM Program
Part A of the trial focuses on evaluating ITM‑94’s safety, biodistribution, and image optimization. Subsequent stages will test ITM‑91 therapy in patients whose tumors express CAIX on ITM‑94 imaging (Part B and C), and assess ITM‑94’s role in classifying indeterminate renal masses (Part D).
The FDA’s fast track designation highlights the potential of ITM‑94 to enhance diagnostic precision and patient selection in clear cell RCC, where noninvasive molecular imaging could complement current CT and MRI standards.
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