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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05706129




Registration number
NCT05706129
Ethics application status
Date submitted
21/12/2022
Date registered
31/01/2023
Date last updated
22/06/2025

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
2022-002573-28
Secondary ID [2] 0 0
Debio 0228-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Clear Cell Renal Cell Cancer (ccRCC) 0 0
Pancreatic Ductal Adenocarcinoma (PDAC) 0 0
Colorectal Cancer (CRC) 0 0
Urothelial Carcinoma (UC) 0 0
Indeterminate Renal Mass (IDRM) 0 0
Muscle Invasive Bladder Cancer (MIBC) 0 0
Head and Neck Cancer (H&N) 0 0
Triple Negative Breast Cancer (TNBC) 0 0
Squamous Non-Small Cell Lung Cancer (NSCLC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - [68Ga]Ga-DPI-4452
Treatment: Drugs - [177Lu]Lu-DPI-4452

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

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.

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.

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

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


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

Treatment: Drugs: [177Lu]Lu-DPI-4452
\[177Lu\]Lu-DPI-4452, administered as IV infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Up to Day 7
Primary outcome [2] 0 0
Part B: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Timepoint [2] 0 0
Cycle 1(each cycle = 28 or 42 days depending on every 4 weeks or 6 weeks dosing schedule)
Primary outcome [3] 0 0
Part C: Objective Response Rate (ORR)
Timepoint [3] 0 0
Up to 81 months
Primary outcome [4] 0 0
Part D: Concordance Between [68Ga]Ga-DPI-4452 Uptake by PET Imaging and Assessment of Histological Characteristics of IDRM
Timepoint [4] 0 0
Day 1
Primary outcome [5] 0 0
Part E: Radiotracer Uptake at Lesion Level Identified by PET Imaging
Timepoint [5] 0 0
Day 1
Secondary outcome [1] 0 0
Part A, B, and C: Concentration of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in Blood and Plasma
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Parts A, B, and C: Concentration of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in Urine
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Part A: Radioligand [68Ga]Ga-DPI-4452 PET Scan Time-Window for Optimal Imaging
Timepoint [3] 0 0
Day 1
Secondary outcome [4] 0 0
Part B: Objective Response Rate (ORR)
Timepoint [4] 0 0
Up to 81 months
Secondary outcome [5] 0 0
Parts B and C: Progression Free Survival (PFS) Rate at 6 Months
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
Parts B and C: Progression Free Survival (PFS)
Timepoint [6] 0 0
Up to 81 months
Secondary outcome [7] 0 0
Parts B and C: Overall Survival (OS)
Timepoint [7] 0 0
Up to 81 months
Secondary outcome [8] 0 0
Parts B and C: Duration of Response (DoR)
Timepoint [8] 0 0
Up to 81 months
Secondary outcome [9] 0 0
Parts B and C: Disease Control Rate (DCR)
Timepoint [9] 0 0
Up to 81 months
Secondary outcome [10] 0 0
Parts B, C, D, and E: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [10] 0 0
Up to 81 months
Secondary outcome [11] 0 0
Parts A, B, C, and E: Number of Positive Tumor Lesions Detected by Imaging
Timepoint [11] 0 0
Part A and E: Day 1; Part B and C: Baseline
Secondary outcome [12] 0 0
Parts A, B, and C: Dosimetry [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452
Timepoint [12] 0 0
Part A: Day 1; Parts B and C: Cycle 1 (each cycle= 28 days)
Secondary outcome [13] 0 0
Part D: Assessment of Diagnostic Accuracy of [68Ga]Ga-DPI-4452 PET imaging
Timepoint [13] 0 0
Day 1

Eligibility
Key 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).
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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, 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2029
Actual
Sample size
Target
270
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
UNSW Sydney, St Vincent's Hospital Sydney - Sydney
Recruitment postcode(s) [1] 0 0
VIC 3000 - Melbourne
Recruitment postcode(s) [2] 0 0
NSW 2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Clermont-Ferrand
Country [2] 0 0
France
State/province [2] 0 0
Dijon
Country [3] 0 0
France
State/province [3] 0 0
Grenoble
Country [4] 0 0
France
State/province [4] 0 0
Lyon Cedex
Country [5] 0 0
France
State/province [5] 0 0
Marseille
Country [6] 0 0
France
State/province [6] 0 0
Nantes
Country [7] 0 0
France
State/province [7] 0 0
Toulouse
Country [8] 0 0
France
State/province [8] 0 0
Vandœuvre-lès-Nancy

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Debiopharm International SA
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Debiopharm International S.A
Address 0 0
Country 0 0
Phone 0 0
+41 21 321 01 11
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05706129