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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
270
\[68Ga\]Ga-DPI-4452, administered as IV injection.
\[177Lu\]Lu-DPI-4452, administered as IV infusion.
Peter MacCallum Cancer Centre
Melbourne, Australia
RECRUITINGUNSW Sydney, St Vincent's Hospital Sydney
Sydney, Australia
RECRUITINGCentre Jean Perrin
Clermont-Ferrand, France
RECRUITINGCentre Georges François Leclerc
Dijon, France
RECRUITINGCHU de Grenoble-Alpes, Boulevard de la Chantourne
Grenoble, France
RECRUITINGCentre Léon Bérard
Lyon, France
RECRUITINGAP-HM - Hopital de la Timone
Marseille, France
RECRUITINGCHU de Nantes
Nantes, France
RECRUITINGIUCT - Oncopole
Toulouse, France
RECRUITINGCHRU de Nancy - Hopitaux de Brabois
Vandœuvre-lès-Nancy, France
RECRUITINGPart A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to Day 7
Part B: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1(each cycle = 28 or 42 days depending on every 4 weeks or 6 weeks dosing schedule)
Part C: Objective Response Rate (ORR)
Time frame: Up to 81 months
Part D: Concordance Between [68Ga]Ga-DPI-4452 Uptake by PET Imaging and Assessment of Histological Characteristics of IDRM
Time frame: Day 1
Part E: Radiotracer Uptake at Lesion Level Identified by PET Imaging
Time frame: Day 1
Part A, B, and C: Concentration of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in Blood and Plasma
Pharmacokinetics (PK) will be evaluated in blood and plasma for radioactivity of \[68Ga\]Ga-DPI-4452 and \[177Lu\]Lu-DPI-4452.
Time frame: Part A: Pre-dose and at multiple time points up to 4 hours post-dose on Day 1; Parts B and C: Pre-dose and at multiple time points up to 72 hours post-dose of Cycles 1, 2 and 3 (84 days) (each cycle = 28 or 42 days depending on every 4 weeks or 6 weeks)
Parts A, B, and C: Concentration of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in Urine
PK will be evaluated in urine for radioactivity of \[68Ga\]Ga-DPI-4452 and \[177Lu\]Lu-DPI-4452.
Time frame: Part A: Pre-dose and at multiple time points up to 4 hours post-dose on Day 1; Parts B and C: Pre-dose and at multiple time points up to 48 hours post-dose of Cycle 1 (each cycle = 28 or 42 days depending on every 4 weeks or 6 weeks dosing schedule)
Part A: Radioligand [68Ga]Ga-DPI-4452 PET Scan Time-Window for Optimal Imaging
Time frame: Day 1
Part B: Objective Response Rate (ORR)
Time frame: Up to 81 months
Parts B and C: Progression Free Survival (PFS) Rate at 6 Months
Time frame: 6 months
Parts B and C: Progression Free Survival (PFS)
Time frame: Up to 81 months
Parts B and C: Overall Survival (OS)
Time frame: Up to 81 months
Parts B and C: Duration of Response (DoR)
Time frame: Up to 81 months
Parts B and C: Disease Control Rate (DCR)
Time frame: Up to 81 months
Parts B, C, D, and E: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to 81 months
Parts A, B, C, and E: Number of Positive Tumor Lesions Detected by Imaging
Time frame: Part A and E: Day 1; Part B and C: Baseline
Parts A, B, and C: Dosimetry [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452
Whole body effective dose will be calculated using the PET scan.
Time frame: Part A: Day 1; Parts B and C: Cycle 1 (each cycle= 28 days)
Part D: Assessment of Diagnostic Accuracy of [68Ga]Ga-DPI-4452 PET imaging
Assessment by sensitivity, specificity, positive predicted value (PPV) and negative predicted value (NPV) of \[68Ga\]Ga-DPI-4452 PET imaging compared to histology.
Time frame: Day 1
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.