ITM Isotope Technologies Munich SE and Debiopharm announced that the first patient was imaged in Part D of their five-part Phase 1/2 clinical trial (NCT05706129) evaluating the theranostic pair ITM-94/ITM-91 for identification and treatment of patients with unresectable, locally advanced or metastatic solid tumors. The new study arm will evaluate ITM-94's effectiveness in classifying indeterminate renal masses as either clear cell renal cell carcinoma (ccRCC) or non-cancerous.
Theranostic Approach Targets CAIX Expression
ITM-91/ITM-94 represents a first-in-class, peptide-based theranostic pair combining the radiotherapeutic compound ITM-91 (Debio 0228) with the diagnostic agent ITM-94 (Debio 0328) to target Carbonic Anhydrase IX (CAIX). CAIX is a cell surface protein that plays a key role in the tumor microenvironment, promoting tumor growth, survival, invasion and metastasis. ITM gained the exclusive worldwide license from Debiopharm for the development and commercial rights of ITM-91/ITM-94 in September 2024.
Study Design and Endpoints
Part D of the trial will evaluate ITM-94's effectiveness to accurately classify an indeterminate renal mass as ccRCC or non-cancerous, when compared to CT/MRI imaging and histopathology. Secondary endpoints include sensitivity, specificity, and the positive and predictive value of ITM-94 PET/CT imaging compared to histopathology. The study arm is expected to enroll approximately 36 patients at around 15 clinical sites across the EU, US and Australia.
Promising Early Results Drive Clinical Expansion
The new study arm builds on promising imaging data demonstrated in Part A of the study for ITM-94, a Gallium-68 (68Ga)-labeled PET imaging candidate. In Part A, ITM-94 demonstrated exceptional tumor imaging characteristics, with a high tumor-to-background ratio and a favorable tolerability profile in patients with confirmed ccRCC, with results published in the Journal of Nuclear Medicine.
"The early results from the Gallium-68 CAIX PET/CT diagnostic are remarkable to date. 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," said Prof. Michael Hofman, Director, Prostate Cancer Theranostics and Imaging Centre of Excellence (ProSTIC), Peter MacCallum Cancer Centre, Melbourne, Australia.
Clinical Significance in Kidney Cancer
Clear cell renal cell carcinoma is the most common form of kidney cancer, with more than 90% of cases overexpressing the CAIX encoding gene. 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," said Dr. Celine Wilke, Chief Medical Officer of ITM.
Comprehensive Clinical Development Program
The five-part clinical trial is designed to assess the safety and tolerability, imaging characteristics, and efficacy of the theranostic pair ITM-91/ITM-94 in patients with unresectable, locally advanced or metastatic solid tumors. Part B, which is ongoing, is assessing escalating doses of the therapeutic agent, ITM-91, in patients whose tumors show high uptake of the imaging tracer. Based on the recommended dose from Part B, Part C of the trial will assess the safety and preliminary efficacy of ITM-91 in patients with ccRCC, pancreatic ductal adenocarcinoma, colorectal cancer, urothelial carcinoma and potentially other tumor types. Part E will assess ITM-94 uptake in other tumors.
"With high-quality imaging and high tumor uptake, ITM-94 has already demonstrated potentially significant diagnostic capabilities in solid tumors. The data gathered in Part D of the trial will be instrumental to the further validation of this theranostic pair," said Angela Zubel, Chief Development Officer, Research & Development at Debiopharm.
ITM-94 is a PET imaging agent that may be used independently and is designed to identify patients whose cancers overexpress CAIX. Once identified, these patients may be treated with the lutetium-labelled radioligand, ITM-91, which delivers targeted radiation to the tumor with the aim to destroy it from the inside. ITM will assume full sponsorship of the program from Debiopharm once the transfer is completed.
