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

NCT05706129 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: ITM-9.4.1.1.01CT2022-002573-282023-504254-35U1111-1289-0392
• Study Type: interventional
• Target: 270
• Locations: 2 countries
• Sites: 10

Brief Summary

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.

Conditions

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)

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (13)

• Part A, B, and C: Concentration of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in Blood and Plasma

  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

  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

Study Arms (5)

Part A: [68Ga]Ga-DPI-4452

EXPERIMENTAL

Participants will receive \[68Ga\]Ga-DPI-4452, a single dose on Day 1.

Drug: [68Ga]Ga-DPI-4452

Part B: [177Lu]Lu-DPI-4452

EXPERIMENTAL

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; Drug: [177Lu]Lu-DPI-4452

Part C: [177Lu]Lu-DPI-4452

EXPERIMENTAL

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; Drug: [177Lu]Lu-DPI-4452

Part D: [68Ga]Ga-DPI-4452

EXPERIMENTAL

Participants will receive \[68Ga\]Ga-DPI-4452, a single dose on Day 1.

Drug: [68Ga]Ga-DPI-4452

Part E: [68Ga]Ga-DPI-4452

EXPERIMENTAL

Participants will receive \[68Ga\]Ga-DPI-4452, a single dose on Day 1.

Drug: [68Ga]Ga-DPI-4452

Interventions

[68Ga]Ga-DPI-4452 DRUG

\[68Ga\]Ga-DPI-4452, administered as IV injection.

Part A: [68Ga]Ga-DPI-4452; Part B: [177Lu]Lu-DPI-4452; Part C: [177Lu]Lu-DPI-4452; Part D: [68Ga]Ga-DPI-4452; Part E: [68Ga]Ga-DPI-4452

[177Lu]Lu-DPI-4452 DRUG

\[177Lu\]Lu-DPI-4452, administered as IV infusion.

Part B: [177Lu]Lu-DPI-4452; Part C: [177Lu]Lu-DPI-4452

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• ITM Oncologics GmbH: lead

Study Sites (10)

Peter MacCallum Cancer Centre

Melbourne, VIC 3000, Australia

RECRUITING

UNSW Sydney, St Vincent's Hospital Sydney

Sydney, NSW 2010, Australia

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

RECRUITING

CHU de Grenoble-Alpes, Boulevard de la Chantourne

Grenoble, 38043, France

RECRUITING

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

AP-HM - Hopital de la Timone

Marseille, 13005, France

RECRUITING

CHU de Nantes

Nantes, 44093, France

RECRUITING

IUCT - Oncopole

Toulouse, 31100, France

RECRUITING

CHRU de Nancy - Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Colorectal Neoplasms; Carcinoma, Transitional Cell; Head and Neck Neoplasms; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

ITM Oncologics GmbH

CONTACT

(+49) 89 329898 66000; info-itm91_94-phase1_2@itm-radiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 31, 2023
• Study Start: March 14, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); FR (8)