FDA Fast Tracks PET Diagnostic Agent for Clear Cell Renal Cell Carcinoma

The FDA has awarded fast track designation to [⁶⁸Ga]Ga-DPI-4452 (ITM-94), a promising noninvasive diagnostic agent for clear cell renal cell carcinoma (ccRCC).¹

Fast track status is granted to novel diagnostic and therapeutic agents aimed at addressing serious unmet medical needs, enabling expedited development and regulatory review.² ccRCC accounts for approximately 75% of malignant kidney cancers and is often characterized by late diagnosis and poor outcomes.³ Current diagnostic approaches rely heavily on CT or MRI, and standard treatment typically consists of moderately invasive surgical interventions. The FDA’s decision was supported by the agent’s noninvasive properties, tumor imaging characteristics, and favorable tolerability profile exhibited in an ongoing phase 1/2 trial (NCT05706129).

[⁶⁸Ga]Ga-DPI-4452 is a gallium-based PET imaging agent that forms a peptide-based theranostic pair with the radiotherapeutic compound [¹⁷⁷Lu]Lu-DPI-4452 (ITM-91). Together, they target the cell surface protein CAIX in the tumor microenvironment, a molecule implicated in tumor growth, survival, invasion, and metastasis.

“The FDA’s [f]ast [t]rack designation is a validation of [(⁶⁸Ga)Ga-DPI-4452]’s potential to aid in the noninvasive diagnosis of [RCC],” said Celine Wilke, MD, chief medical officer of ITM Isotope Technologies, in a news release.¹ “We have seen promising data in our ongoing clinical trial that suggest [(⁶⁸Ga)Ga-DPI-4452] could change how clinicians diagnose and stage patients across the broader ccRCC disease landscape, with potential utility in supporting clinical decision-making for indeterminate renal masses as well. This news highlights the innovation within our pipeline and the important role an effective diagnostic can play in cancer treatment.”

About the Phase 1/2 Trial

The supporting phase 1/2 trial is an open-label, nonrandomized study assessing the safety, tolerability, imaging characteristics, and efficacy of the theranostic pair in patients with unresectable, locally advanced or metastatic solid tumors.⁴

The trial is currently recruiting for an estimated total enrollment of 270 patients across various cancers, including ccRCC, pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), urothelial cancer, muscle-invasive bladder cancer, head and neck cancer, triple-negative breast cancer, and squamous non–small cell lung cancer.

For patients with ccRCC, eligibility criteria include receipt of at least 2 lines of treatment in the metastatic setting, including 1 prior line of tyrosine kinase inhibitor treatment and at least 1 line containing immune checkpoint inhibitor treatment. In addition, they must have had imaging evidence of a single indeterminate renal mass of at least 7 cm in largest diameter within 90 days from planned [⁶⁸Ga]Ga-DPI-4452 administration.

The trial consists of 5 parts:

1. Part A: Evaluating the safety, tolerability, and tracer uptake following a single intravenous administration of the diagnostic agent, [⁶⁸Ga]Ga-DPI-4452, for each tumor type.
2. Part B (dose escalation): Assessing increasing doses of the therapeutic agent, [¹⁷⁷Lu]Lu-DPI-4452, and establishing the recommended phase 2 dose (RP2D) for each CAIX-expressing tumor type.
3. Part C (dose expansion): Evaluating the safety and preliminary antitumor activity of [¹⁷⁷Lu]Lu-DPI-4452 as monotherapy for each tumor type.
4. Part D: Evaluating the effectiveness of [⁶⁸Ga]Ga-DPI-4452 in classifying indeterminate renal masses (eg, ccRCC) compared with CT/MRI.
5. Part E: Assessing the uptake of [⁶⁸Ga]Ga-DPI-4452 in each tumor type excluding ccRCC, CRC, and PDAC.

REFERENCES

1. ITM receives U.S. FDA fast track designation for ITM-94 as a diagnostic agent for clear cell renal cell carcinoma. News release. ITM Isotope Technologies Munich SE. November 17, 2025. Accessed November 17, 2025. https://tinyurl.com/3txmzrw5

2. Fast track. FDA. Updated August 13, 2024. Accessed November 17, 2025. https://tinyurl.com/ms2695jn

3. Quinn AE, Bell SD, Marrah AJ, et al. The current state of the diagnoses and treatments for clear cell renal cell carcinoma. Cancers (Basel). 2024;16(23):4034. Published 2024 Dec 1. doi:10.3390/cancers16234034

4. 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. Updated October 20, 2025. Accessed November 17, 2025. https://clinicaltrials.gov/study/NCT05706129