Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1/Phase 2
Debiopharm International SA (Voir sur ClinicalTrials)
mars 2023
mars 2029
24 juin 2025
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.
Etablissements
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HM - Hopital de la Timone - 13005 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Centre Georges François Leclerc - 21079 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Jean Perrin - 63011 - Clermont-Ferrand - France | Contact (sur clinicalTrials) | ||||
| Centre Léon Bérard - 69373 - Lyon Cedex - France | Contact (sur clinicalTrials) | ||||
| CHRU de Nancy - Hopitaux de Brabois - 54511 - Vandœuvre-lès-Nancy - France | Contact (sur clinicalTrials) | ||||
| CHU de Grenoble-Alpes, Boulevard de la Chantourne - 38043 - Grenoble - France | Contact (sur clinicalTrials) | ||||
| CHU de Nantes - 44093 - Nantes - France | Contact (sur clinicalTrials) | ||||
| IUCT - Oncopole - 31100 - Toulouse - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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.
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.
- 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.