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

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.

Study Overview

• Status: Recruiting
• Conditions: Triple Negative Breast Cancer (TNBC); Pancreatic Ductal Adenocarcinoma (PDAC); Colorectal Cancer (CRC); Clear Cell Renal Cell Cancer (ccRCC); Urothelial Carcinoma (UC); Indeterminate Renal Mass (IDRM); Muscle Invasive Bladder Cancer (MIBC); Head and Neck Cancer (H&N); Squamous Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: [68Ga]Ga-DPI-4452; Drug: [177Lu]Lu-DPI-4452

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: ITM Oncologics GmbH; Phone Number: (+49) 89 329898 66000; Email: info-itm91_94-phase1_2@itm-radiopharma.com

Study Locations

• Australia
  • Melbourne, Australia, VIC 3000
    • Recruiting
    • Peter MacCallum Cancer Centre
  • Sydney, Australia, NSW 2010
    • Recruiting
    • UNSW Sydney, St Vincent's Hospital Sydney
• France
  • Clermont-Ferrand, France, 63011
    • Recruiting
    • Centre Jean Perrin
  • Dijon, France, 21079
    • Recruiting
    • Centre Georges Francois Leclerc
  • Grenoble, France, 38043
    • Recruiting
    • CHU de Grenoble-Alpes, Boulevard de la Chantourne
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
  • Marseille, France, 13005
    • Recruiting
    • AP-HM - Hôpital de la Timone
  • Nantes, France, 44093
    • Recruiting
    • CHU de Nantes
  • Toulouse, France, 31100
    • Recruiting
    • IUCT - Oncopole
  • Vandœuvre-lès-Nancy, France, 54511
    • Recruiting
    • CHRU de Nancy - Hopitaux de Brabois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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).
• For Part B and C only: Urothelial cancer (UC) patients must have received all available standard of care if eligible, including one line of platinum-based chemotherapy, enfortumab vedotin and pembrolizumab.
• 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.

Presence of at least 1 non-irradiated tumor lesion detected at conventional imaging (CT/MRI) documented within 4 weeks prior to the [68Ga]Ga-DPI-4452 administration (for scans dated more than 4 weeks prior to D1, the Sponsor should be contacted to assess conventional imaging suitability)

Exclusion Criteria:

• 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.

Part A:

• 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.

Part B and Part C:

• 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, active clinically significant cardiac disease, 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).

Part D:

• 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.

Part E:

• 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.

Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	Measure Description	Time Frame
Parts B and C: Progression Free Survival (PFS) Rate at 6 Months		6 months
Part B: Objective Response Rate (ORR)		Up to 81 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
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
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

Collaborators and Investigators

• Sponsor: ITM Oncologics GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 16, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Colonic Diseases; Skin Diseases; Breast Diseases; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Breast Neoplasms; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Carcinoma, Renal Cell; Head and Neck Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Transitional Cell
• Other Study ID Numbers: ITM-9.4.1.1.01CT; 2022-002573-28 (EudraCT Number); 2023-504254-35 (Other Identifier: EU CT Number); U1111-1289-0392 (Other Identifier: WHO Unique Trial Identifier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No