A Multicenter, Open-Label, Non-Randomized Phase 1/2 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 Patients With Unresectable Locally Advanced or Metastatic Solid Tumors
The main purpose of Part A of the study is to evaluate safety, tolerability and tracer uptake after a single intravenous (IV) administration of \[68Ga\]Ga-DPI-4452 for each tumor type such as clear cell renal cell cancer (ccRCC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC); Part B: is to determine the recommended phase 2 dose (RP2D) \[maximum tolerated dose (MTD) or lower dose\] for \[177Lu\]Lu-DPI-4452 for each tumor type such as ccRCC, PDAC, CRC, and urothelial carcinoma (UC); Part C: is to evaluate the preliminary antitumor activity of \[177Lu\]Lu-DPI-4452 as monotherapy for each tumor type such as ccRCC, PDAC, CRC, and UC; Part D: is to assess the diagnostic concordance between \[68Ga\]Ga-DPI-4452 Positron Emission Tomography (PET) and the histopathology result of the Indeterminate Renal Mass (IDRM); Part E: is to assess \[68Ga\]Ga-DPI-4452 uptake in each tumour type such as UC, muscle invasive bladder cancer (MIBC), head and neck cancer (H\&N), triple negative breast cancer (TNBC), squamous non-small cell lung cancer (NSCLC), and any other tumor with locally confirmed carbonic anhydrase (CA) IX expression except ccRCC, CRC and PDAC.
⁃ Part A, B, and C:
• Written informed consent, dated and signed by the patient prior to any study-specific procedure.
• Part B and C are not conducted in the United States of America.
• Has histologically or cytologically confirmed, unresectable locally advanced or metastatic solid tumors of:
• Clear cell renal cell cancer (ccRCC) - participants must have received at least one line containing Tyrosine kinase inhibitor (TKI) treatment and at least one line containing immune checkpoint inhibitor treatment in metastatic setting, meaning at least two lines of treatment in metastatic setting.
• Pancreatic ductal adenocarcinoma (PDAC) - participants must have received at least one line of platinum- and/or gemcitabine-based regimen.
• Colorectal cancer (CRC) - participants must have received at least one line of FOLFIRINOX or FOLFOX/FOLFIRI in two lines in combination with anti-Vascular Endothelial Growth Factor (VEGF) or anti-Epidermal Growth Factor Receptor (EGFR).
• Participants with CRC or PDAC: availability of fresh biopsy, OR an archival biopsy/surgical specimen of the tumor (preferably, taken after last prior line of therapy).
• Presence of at least 1 non-irradiated tumor lesion detected at conventional imaging (computed tomography / magnetic resonance imaging (CT/MRI)) documented within 4 weeks prior to the \[68Ga\]Ga-DPI-4452 administration.
• Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1.
⁃ Part D:
⁃ Participants with imaging evidence of a single indeterminate renal mass (IDRM) of ≤ 7 cm in largest diameter (tumor stage cT1) on any conventional diagnostic imaging technique, suspicious for ccRCC and planned for total or partial nephrectomy, or interventional diagnostic (cystoscopy and retrograde pyelography or biopsy) within 90 days from planned \[68Ga\]Ga-DPI-4452 administration.
⁃ Part E:
⁃ Regardless of lines of treatment, participants with histologically or cytologically confirmed progressive, unresectable locally advanced or metastatic solid tumors of
• UC, including MIBC
• H\&N cancer
• TNBC
• Squamous NSCLC
• Any other indication with confirmed carbonic anhydrase IX (CA IX) expression excluding ccRCC, PDAC and CRC, upon Sponsor agreement.