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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05706129




Registration number
NCT05706129
Ethics application status
Date submitted
21/12/2022
Date registered
31/01/2023
Date last updated
29/03/2024

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
Condition category
Condition code
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 28-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 28-day cycle during the treatment period.


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 (28 days)
Primary outcome [3] 0 0
Part C: Objective Response Rate (ORR)
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
Part A: Concentration of [68Ga]Ga-DPI-4452 in Blood
Timepoint [1] 0 0
Pre-dose and at multiple time points up to 4 hours post-dose on Day 1
Secondary outcome [2] 0 0
Part A: Radioligand [68Ga]Ga-DPI-4452 Positron Emission Tomography (PET) Scan Time-Window for Optimal Imaging
Timepoint [2] 0 0
Day 1
Secondary outcome [3] 0 0
Part B: Objective Response Rate (ORR)
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
Parts B and C: Concentration of [177Lu]Lu-DPI-4452 in Blood and Plasma
Timepoint [4] 0 0
Pre-dose and at multiple time points up to 72 hours post-dose of Cycles 1, 2 and 3 (84 days) {each cycle= 28 days}
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 approximately 2 years
Secondary outcome [7] 0 0
Parts B and C: Overall Survival (OS)
Timepoint [7] 0 0
Up to approximately 2 years
Secondary outcome [8] 0 0
Parts B and C: Duration of Response (DoR)
Timepoint [8] 0 0
Up to approximately 2 years
Secondary outcome [9] 0 0
Parts B and C: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [9] 0 0
Up to approximately 2 years
Secondary outcome [10] 0 0
Parts A, B and C: Concentration of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in Urine
Timepoint [10] 0 0
Part A: Pre-dose and at multiple time points up to 4 hours post-dose on Day 1; Part B: Cycle 1 (each cycle= 28 days); Part C: Pre-dose and at multiple time points up to 24 hours post-dose of Cycle 1 (each cycle= 28 days)
Secondary outcome [11] 0 0
Parts A, B and C: Number of Positive Tumor Lesions Detected by Imaging
Timepoint [11] 0 0
Part A: Day 1; Part B and C: Baseline
Secondary outcome [12] 0 0
Parts B and C: Disease Control Rate (DCR)
Timepoint [12] 0 0
Up to approximately 2 years
Secondary outcome [13] 0 0
Parts A, B and C: Human Dosimetry [68Ga]Ga-DPI-4452
Timepoint [13] 0 0
Part A: Day 1; Parts B and C: Cycle 1 (each cycle= 28 days)

Eligibility
Key inclusion criteria
Part A, B and C:

- Written informed consent, dated and signed by the patient prior to any study-specific
procedure

- 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; or

- 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
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 enrollment

- 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 more than 1 cycle or 1 month.

- 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).

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/Phase 2
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
1/01/2027
Actual
Sample size
Target
155
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
Lyon Cedex
Country [3] 0 0
France
State/province [3] 0 0
Marseille
Country [4] 0 0
France
State/province [4] 0 0
Nantes
Country [5] 0 0
France
State/province [5] 0 0
Toulouse
Country [6] 0 0
France
State/province [6] 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
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; 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; Part C: is to evaluate the preliminary antitumor
activity of [177Lu]Lu-DPI-4452 as monotherapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05706129
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
clinicaltrials@debiopharm.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05706129