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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

Phase 1
Recruiting
Conditions
Clear Cell Renal Cell Cancer (ccRCC)
Pancreatic Ductal Adenocarcinoma (PDAC)
Colorectal Cancer (CRC)
Registration Number
NCT05706129
Lead Sponsor
Debiopharm International SA
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
170
Inclusion Criteria

Inclusion Criteria:<br><br>Part A, B and C:<br><br> - Written informed consent, dated and signed by the patient prior to any<br> study-specific procedure<br><br> - Has histologically or cytologically confirmed, unresectable locally advanced or<br> metastatic solid tumors of:<br><br> - clear cell renal cell cancer (ccRCC) - participants must have received at least one<br> line containing Tyrosine kinase inhibitor (TKI) treatment and at least one line<br> containing Immune Checkpoint Inhibitor treatment in metastatic setting, meaning at<br> least two lines of treatment in metastatic setting,<br><br> - pancreatic ductal adenocarcinoma (PDAC) - participants must have received at least<br> one line of platinum- and/or gemcitabine based regimen; or<br><br> - colorectal cancer (CRC) - participants must have received at least one line of<br> FOLFIRINOX or FOLFOX/FOLFIRI in two lines in combination with anti-Vascular<br> Endothelial Growth Factor (VEGF) or anti-Epidermal Growth Factor Receptor (EGFR).<br><br> - Participants with CRC or PDAC: availability of fresh biopsy, OR an archival<br> biopsy/surgical specimen of the tumor (preferably, taken after last prior line of<br> therapy).<br><br> - Presence of at least 1 non-irradiated tumor lesion detected at conventional imaging<br> (computed tomography / magnetic resonance imaging (CT/MRI)) documented within 4<br> weeks prior to the [68Ga]Ga-DPI-4452 administration.<br><br> - Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1<br><br>Exclusion Criteria:<br><br> - Any major surgery within 12 weeks before enrollment<br><br> - Inability to stay in the scanner bed with the arms resting out of the thoracic and<br> abdominal fields (i.e., arms alongside the body or raised arm position) for the<br> duration of the scan<br><br>Part A:<br><br> - Has known hypersensitivity to the active substance, to any of the excipients of the<br> DPI-4452, or to radiographic contrast agents.<br><br> - Bladder outflow obstruction or unmanageable urinary incontinence.<br><br> - Participants who have not had resolution of clinically significant toxic effects of<br> prior systemic cancer therapy, surgery, or radiotherapy to Grade =1 (except for<br> laboratory parameters specified above, Grade 2 alopecia, and/or stable Grade 2<br> sensory neuropathy, according to National Cancer Institute Common Terminology<br> Criteria for Adverse Events [NCI-CTCAE]).<br><br> - Administration of a radiopharmaceutical within a period corresponding to 10<br> half-lives of the radionuclide used prior to injection of [68Ga]Ga-DPI-4452.<br><br> - Previous Carbonic anhydrase (CA) IX-targeting treatment.<br><br> - Prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow, as<br> judged by the Investigator.<br><br>Part B and Part C:<br><br> - Known hypersensitivity to the active substance, to any of the excipients of the<br> DPI-4452, or to radiographic contrast agents.<br><br> - Bladder outflow obstruction or unmanageable urinary incontinence.<br><br> - Participants who have not had resolution of clinically significant toxic effects of<br> prior systemic cancer therapy, surgery, or radiotherapy to Grade =1 (except for<br> laboratory parameters specified above, Grade 2 alopecia, or stable Grade 2 sensory<br> neuropathy, according to NCI-CTCAE).<br><br> - Administration of a radiopharmaceutical with therapeutic intent within a period of 6<br> months prior to injection of [68Ga]Ga-DPI-4452.<br><br> - Any previous CA IX-targeting treatment for more than 1 cycle or 1 month.<br><br> - Participants who received any systemic antineoplastic therapy for the underlying<br> disease and/or other investigational agents within a period which is =5 half-lives<br> or =4 weeks (whichever is shorter).<br><br> - Inflammatory bowel disease (e.g Crohn's disease, ulcerative colitis, etc).<br><br>Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.

Exclusion Criteria

Not provided

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs);Part B: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs);Part C: Objective Response Rate (ORR)
Secondary Outcome Measures
NameTimeMethod
Part A: Concentration of [68Ga]Ga-DPI-4452 in Blood;Part A: Radioligand [68Ga]Ga-DPI-4452 Positron Emission Tomography (PET) Scan Time-Window for Optimal Imaging;Part B: Objective Response Rate (ORR);Parts B and C: Concentration of [177Lu]Lu-DPI-4452 in Blood and Plasma;Parts B and C: Progression Free Survival (PFS) Rate at 6 Months;Parts B and C: Progression Free Survival (PFS);Parts B and C: Overall Survival (OS);Parts B and C: Duration of Response (DoR);Parts B and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs);Parts A, B and C: Concentration of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in Urine;Parts A, B and C: Number of Positive Tumor Lesions Detected by Imaging;Parts B and C: Disease Control Rate (DCR);Parts A, B and C: Human Dosimetry [68Ga]Ga-DPI-4452
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