Trial launches of diagnostic agent for clear cell renal cell carcinoma

The first patient has been imaged in part D of a phase 1/2 trial (NCT05706129), evaluating the efficacy of the diagnostic agent ITM-94 (Debio 0328; [68Ga]Ga-DPI-4452) in detecting clear cell renal cell carcinoma (ccRCC) in patients with an indeterminate renal mass (IDRM).¹

The primary outcome measure is the concordance between [68Ga]Ga-DPI-4452 and CT/MRI imaging and histopathology.

Overall, the phase 1/2 trial is assessing the safety and efficacy of the theranostic pair ITM-94/ITM-91 in identifying and treating patients with unresectable, locally advanced or metastatic solid tumors. The radiotherapeutic compound ITM-91 (Debio 0228; [177Lu]Lu-DPI-4452) works with the diagnostic agent ITM-94 to target carbonic anhydrase IX (CAIX), a cell surface protein that plays a key role in the tumor microenvironment.

In total, the phase 1/2 trial plans to enroll 270 patients across 5 study arms.² Arm D is expected to enroll approximately 36 patients across 15 clinical trial sites in the US, EU, and Australia.

To be eligible for enrollment, patients need to have an IDRM with a largest diameter of 7 cm or smaller (stage cT1) that is suspicious for ccRCC and planned for total or partial nephrectomy or interventional diagnostic within 90 days from planned [68Ga]Ga-DPI-4452 administration.

The primary outcome measure for arm D is the concordance between [68Ga]Ga-DPI-4452 and CT/MRI imaging and histopathology in classifying IDRM as cancerous or non-cancerous. Secondary end points in the study include sensitivity, specificity, and the positive predictive value of [68Ga]Ga-DPI-4452 PET/CT imaging compared with histopathology.

“The early results from the Gallium-68 CAIX PET/CT diagnostic are remarkable to date,” said Michael S. Hofman, MBBS, FRACP, FAANMS, FICIS, GAICD, Director, Prostate Cancer Theranostics and Imaging Centre of Excellence (ProSTIC) at the Peter MacCallum Cancer Centre in Melbourne, Australia, in the news release.¹ “I believe ITM-94 has the potential to change the way urologists and oncologists diagnose and stage patients with clear cell renal cell carcinoma, improving accuracy and reducing the need for biopsies. I have not seen a tracer with a similar profile since the PSMA PET/CT was established.”

About the Phase 1/2 Trial

In addition to part D, part A of the study evaluated the safety, tolerability, and tracer uptake of [68Ga]Ga-DPI-4452 across several tumor types, including ccRCC. Data showed “exceptional tumor imaging characteristics, with a high tumor-to-background ratio and a favorable tolerability profile in patients with confirmed ccRCC,” according to ITM and Debiopharm.¹ Specifically, tumor uptake was observed across all time points, ranging from 15 min to 4 hours. The SUV_max at 1 hour following administration ranged from 6.8 to 211.6 (mean, 64.6; SD, 54.8).³

Part B of the trial is ongoing and is assessing escalating doses of [177Lu]Lu-DPI-4452 in patients whose tumors show high uptake of the imaging tracer. The recommended dose from Part B of the trial will be used to inform part C, which will further assess the safety and preliminary efficacy of [177Lu]Lu-DPI-4452 in patients with ccRCC, urothelial carcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, and potentially other tumor types. Part E of the trial will assess uptake of [68Ga]Ga-DPI-4452 in other malignancies beyond ccRCC, including urothelial carcinoma, muscle–invasive bladder cancer, and other tumors expressing CAIX.

Primary completion of the trial is anticipated for June 2027.

“Clear cell renal cell carcinoma is the most common form of kidney cancer, with more than 90% of cases overexpressing the CAIX encoding gene,” said Celine Wilke, MD, Chief Medical Officer of ITM, in the news release.¹ “As survival rates are highly dependent on the stage of progression, rapid and precise diagnosis is essential to provide patients with the best possible treatment options and therapeutic outcomes. ITM-94 has already demonstrated potential exceptional imaging qualities, including high tumor-to-background ratios and detecting lesions not visible by CT scan with a potential favorable safety profile. We look forward to exploring the full potential of the theranostic pair ITM-91/ITM-94 across this trial to characterize and treat CAIX expressing cancer cells, advancing the efficacy of targeted radiopharmaceutical therapies.”

REFERENCES

1. ITM and Debiopharm announce first patient imaged in new study arm of phase 1/2 trial evaluating ITM-94 as diagnostic agent for clear cell renal cell carcinoma (ccRCC). News release. ITM Isotope Technologies Munich SE. Published online and accessed June 23, 2025. https://www.globenewswire.com/news-release/2025/06/23/3103185/0/en/ITM-and-Debiopharm-Announce-First-Patient-Imaged-in-New-Study-Arm-of-Phase-1-2-Trial-Evaluating-ITM-94-as-Diagnostic-Agent-for-Clear-Cell-Renal-Cell-Carcinoma-ccRCC.html

2. A Study to Assess Safety, Tolerability and Imaging Characteristics of [68Ga]Ga-DPI-4452 and to Assess Safety, Tolerability, and Efficacy of [177Lu]Lu-DPI-4452 in Participants With Unresectable Locally Advanced or Metastatic Solid Tumors. ClinicalTrials.gov. Last updated June 22, 2025. Accessed June 23, 2025. https://clinicaltrials.gov/study/NCT05706129

3. Hofman MS, Tran B, Feldman DR, et al. First-in-human safety, imaging, and dosimetry of a carbonic anhydrase IX–targeting peptide, [68Ga]Ga-DPI-4452, in patients with clear cell renal cell carcinoma. J Nucl Med. 2024;65 (5) 740-743. doi:10.2967/jnumed.123.267175