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

Study Overview

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

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.

N/A

Clear Cell Renal Cell Cancer (ccRCC)
Pancreatic Ductal Adenocarcinoma (PDAC)
Colorectal Cancer (CRC)
Urothelial Carcinoma (UC)
Indeterminate Renal Mass (IDRM)
Muscle Invasive Bladder Cancer (MIBC)
Head and Neck Cancer (H&N)
Triple Negative Breast Cancer (TNBC)
Squamous Non-Small Cell Lung Cancer (NSCLC)

DRUG: [68Ga]Ga-DPI-4452
DRUG: [177Lu]Lu-DPI-4452

Debio 0228-101
2022-002573-28 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )
2023-504254-35 (OTHER Identifier) (OTHER: EU CT Number)
U1111-1289-0392 (OTHER Identifier) (OTHER: WHO Unique Trial Identifier)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-12-21	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-06-20
First Submitted that Met QC Criteria 2023-01-20	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-06-22
First Posted (ACTUAL) 2023-01-31	Results First Posted N/A	Last Verified 2025-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Part A: [68Ga]Ga-DPI-4452 Participants will receive [68Ga]Ga-DPI-4452, a single dose on Day 1.	DRUG: [68Ga]Ga-DPI-4452 [68Ga]Ga-DPI-4452, administered as IV injection.
EXPERIMENTAL: Part B: [177Lu]Lu-DPI-4452 Participants will receive a single dose of [68Ga]Ga-DPI-4452, at screening then escalating doses of [177Lu]Lu-DPI-4452, on Day 1 of each (Q4W or Q6W) cycle and RP2D will be determined.	DRUG: [68Ga]Ga-DPI-4452 [68Ga]Ga-DPI-4452, administered as IV injection. DRUG: [177Lu]Lu-DPI-4452 [177Lu]Lu-DPI-4452, administered as IV infusion.
EXPERIMENTAL: Part C: [177Lu]Lu-DPI-4452 Participants will receive a single dose of [68Ga]Ga-DPI-4452, at screening and RP2D dose of [177Lu]Lu-DPI-4452, on Day 1 of each cycle (Q4W or Q6W) the treatment period.	DRUG: [68Ga]Ga-DPI-4452 [68Ga]Ga-DPI-4452, administered as IV injection. DRUG: [177Lu]Lu-DPI-4452 [177Lu]Lu-DPI-4452, administered as IV infusion.
EXPERIMENTAL: Part D: [68Ga]Ga-DPI-4452 Participants will receive [68Ga]Ga-DPI-4452, a single dose on Day 1.	DRUG: [68Ga]Ga-DPI-4452 [68Ga]Ga-DPI-4452, administered as IV injection.
EXPERIMENTAL: Part E: [68Ga]Ga-DPI-4452 Participants will receive [68Ga]Ga-DPI-4452, a single dose on Day 1.	DRUG: [68Ga]Ga-DPI-4452 [68Ga]Ga-DPI-4452, administered as IV injection.

Primary Outcome Measures	Measure Description	Time Frame
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Up to Day 7
Part B: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)		Cycle 1(each cycle = 28 or 42 days depending on every 4 weeks or 6 weeks dosing schedule)
Part C: Objective Response Rate (ORR)		Up to 81 months
Part D: Concordance Between [68Ga]Ga-DPI-4452 Uptake by PET Imaging and Assessment of Histological Characteristics of IDRM		Day 1
Part E: Radiotracer Uptake at Lesion Level Identified by PET Imaging		Day 1

Secondary Outcome Measures	Measure Description	Time Frame
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.	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.	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		Day 1
Part B: Objective Response Rate (ORR)		Up to 81 months
Parts B and C: Progression Free Survival (PFS) Rate at 6 Months		6 months
Parts B and C: Progression Free Survival (PFS)		Up to 81 months
Parts B and C: Overall Survival (OS)		Up to 81 months
Parts B and C: Duration of Response (DoR)		Up to 81 months
Parts B and C: Disease Control Rate (DCR)		Up to 81 months
Parts B, C, D, and E: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Up to 81 months
Parts A, B, C, and E: Number of Positive Tumor Lesions Detected by Imaging		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.	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.	Day 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Debiopharm International S.A

Phone Number: +41 21 321 01 11

Email: clinicaltrials@debiopharm.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Any major surgery within 12 weeks before enrolment.
Inability to stay in the scanner bed with the arms resting out of the thoracic and abdominal fields (i.e., arms alongside the body or raised arm position) for the duration of the scan.

Has known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
Bladder outflow obstruction or unmanageable urinary incontinence.
Participants who have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 (except for laboratory parameters specified above, Grade 2 alopecia, and/or stable Grade 2 sensory neuropathy, according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]).
Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of [68Ga]Ga-DPI-4452.
Previous Carbonic anhydrase (CA) IX-targeting treatment.
Prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow, as judged by the Investigator.

Known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
Bladder outflow obstruction or unmanageable urinary incontinence.
Participants who have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 (except for laboratory parameters specified above, Grade 2 alopecia, or stable Grade 2 sensory neuropathy, according to NCI-CTCAE).
Administration of a radiopharmaceutical with therapeutic intent within a period of 6 months prior to injection of [68Ga]Ga-DPI-4452.
Any previous CA IX-targeting treatment for non-oncological indication within 3 months prior to the [177Lu]Lu-DPI-4452 infusion; any previous CA IX-targeting treatment for any oncological indication.
Participants who received any systemic antineoplastic therapy for the underlying disease and/or other investigational agents within a period which is ≤5 half-lives or ≤4 weeks (whichever is shorter).
Inflammatory bowel disease (e.g Crohn's disease, ulcerative colitis, etc).

Known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
Any previous CA IX-targeting treatment within 3 months prior to the [68Ga]Ga-DPI-4452 injection.
Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of [68Ga]Ga-DPI-4452.
Malignant disease, other than that being treated in this study. Exceptions include the following: malignancies that were treated curatively and have not recurred within 2 years prior to screening; treated basal cell or localized squamous skin carcinomas, localized or low grade (e.g., Gleason 3+3 or 3+4 with low prostate specific antigen) prostate cancer, superficial (non-muscle invasive) urothelial cancer, localized thyroid gland microcarcinoma, other in-situ carcinoma, or other malignancy for which participants are not on active antineoplastic therapy.
Ongoing treatment with sulfonamides and/or coumarin derivatives (e.g., acenocoumarol, warfarin, phenprocoumon) within 2 weeks (or 5 half-lives, whichever is longer) prior to the [68Ga]Ga-DPI-4452 injection.

Known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of [68Ga]Ga-DPI-4452.
Any previous CA IX-targeting treatment within 3 months prior to [68Ga]Ga-DPI-4452 injection.
EBRT to more than 25% of the bone marrow, as judged by the Investigator.
Malignant disease, other than that being treated in this study. Exceptions include the following: malignancies that were treated curatively and have not recurred within 2 years prior to screening; treated basal cell or localized squamous skin carcinomas, localized or low grade (e.g., Gleason 3+3 or 3+4 with low prostate specific antigen) prostate cancer, superficial (non-muscle invasive) urothelial cancer, localized thyroid gland microcarcinoma, other in-situ carcinoma, or other malignancy for which participants are not on active antineoplastic therapy.

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