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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

Primary Purpose

Clear Cell Renal Cell Cancer (ccRCC), Pancreatic Ductal Adenocarcinoma (PDAC), Colorectal Cancer (CRC)

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
[68Ga]Ga-DPI-4452
[177Lu]Lu-DPI-4452
Sponsored by
Debiopharm International SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clear Cell Renal Cell Cancer (ccRCC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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.

Sites / Locations

  • Peter MacCallum Cancer CentreRecruiting
  • UNSW Sydney, St Vincent's Hospital SydneyRecruiting
  • Centre Jean PerrinRecruiting
  • CHU de Nantes
  • CHRU de Nancy - Hopitaux de BraboisRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

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

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

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

Arm Description

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

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.

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.

Outcomes

Primary Outcome Measures

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Part B: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Part C: Objective Response Rate (ORR)

Secondary Outcome Measures

Part A: Concentration of [68Ga]Ga-DPI-4452 in Blood
Pharmacokinetics (PK) will be evaluated in blood for radioactivity of [68Ga]Ga-DPI-4452.
Part A: Radioligand [68Ga]Ga-DPI-4452 Positron Emission Tomography (PET) Scan Time-Window for Optimal Imaging
Part B: Objective Response Rate (ORR)
Parts B and C: Concentration of [177Lu]Lu-DPI-4452 in Blood and Plasma
PK will be evaluated in blood and plasma for radioactivity of [177Lu]Lu-DPI-4452.
Parts B and C: Progression Free Survival (PFS) Rate at 6 Months
Parts B and C: Progression Free Survival (PFS)
Parts B and C: Overall Survival (OS)
Parts B and C: Duration of Response (DoR)
Parts B and C: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Parts A, B and C: Number of Positive Tumor Lesions Detected by Imaging
Parts B and C: Disease Control Rate (DCR)
Parts A, B and C: Human Dosimetry [68Ga]Ga-DPI-4452
Whole body effective dose will be calculated using the PET scan.

Full Information

First Posted
December 21, 2022
Last Updated
August 25, 2023
Sponsor
Debiopharm International SA
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1. Study Identification

Unique Protocol Identification Number
NCT05706129
Brief 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
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 14, 2023 (Actual)
Primary Completion Date
January 2026 (Anticipated)
Study Completion Date
January 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Debiopharm International SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clear Cell Renal Cell Cancer (ccRCC), Pancreatic Ductal Adenocarcinoma (PDAC), Colorectal Cancer (CRC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
147 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A: [68Ga]Ga-DPI-4452
Arm Type
Experimental
Arm Description
Participants will receive [68Ga]Ga-DPI-4452, a single dose on Day 1.
Arm Title
Part B: [177Lu]Lu-DPI-4452
Arm Type
Experimental
Arm Description
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.
Arm Title
Part C: [177Lu]Lu-DPI-4452
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
[68Ga]Ga-DPI-4452
Intervention Description
[68Ga]Ga-DPI-4452, administered as IV injection.
Intervention Type
Drug
Intervention Name(s)
[177Lu]Lu-DPI-4452
Intervention Description
[177Lu]Lu-DPI-4452, administered as IV infusion.
Primary Outcome Measure Information:
Title
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame
Up to Day 7
Title
Part B: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time Frame
Cycle 1 (28 days)
Title
Part C: Objective Response Rate (ORR)
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Part A: Concentration of [68Ga]Ga-DPI-4452 in Blood
Description
Pharmacokinetics (PK) will be evaluated in blood for radioactivity of [68Ga]Ga-DPI-4452.
Time Frame
Pre-dose and at multiple time points 6 hours post-dose on Day 1
Title
Part A: Radioligand [68Ga]Ga-DPI-4452 Positron Emission Tomography (PET) Scan Time-Window for Optimal Imaging
Time Frame
Day 1
Title
Part B: Objective Response Rate (ORR)
Time Frame
Up to approximately 2 years
Title
Parts B and C: Concentration of [177Lu]Lu-DPI-4452 in Blood and Plasma
Description
PK will be evaluated in blood and plasma for radioactivity of [177Lu]Lu-DPI-4452.
Time Frame
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}
Title
Parts B and C: Progression Free Survival (PFS) Rate at 6 Months
Time Frame
6 months
Title
Parts B and C: Progression Free Survival (PFS)
Time Frame
Up to approximately 2 years
Title
Parts B and C: Overall Survival (OS)
Time Frame
Up to approximately 2 years
Title
Parts B and C: Duration of Response (DoR)
Time Frame
Up to approximately 2 years
Title
Parts B and C: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame
Up to approximately 2 years
Title
Parts A, B and C: Concentration of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in Urine
Description
PK will be evaluated in urine for radioactivity of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452.
Time Frame
Part A: Pre-dose and at multiple time points 6 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 72 hours post-dose of Cycle 1 (each cycle= 28 days)
Title
Parts A, B and C: Number of Positive Tumor Lesions Detected by Imaging
Time Frame
Part A: Day 1; Part B and C: Baseline
Title
Parts B and C: Disease Control Rate (DCR)
Time Frame
Up to approximately 2 years
Title
Parts A, B and C: Human Dosimetry [68Ga]Ga-DPI-4452
Description
Whole body effective dose will be calculated using the PET scan.
Time Frame
Part A: Day 1; Parts B and C: Cycle 1 (each cycle= 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Debiopharm International S.A
Phone
+41 21 321 01 11
Email
clinicaltrials@debiopharm.com
Facility Information:
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
ZIP/Postal Code
VIC 3000
Country
Australia
Individual Site Status
Recruiting
Facility Name
UNSW Sydney, St Vincent's Hospital Sydney
City
Sydney
ZIP/Postal Code
NSW 2010
Country
Australia
Individual Site Status
Recruiting
Facility Name
Centre Jean Perrin
City
Clermont-Ferrand
ZIP/Postal Code
63011
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Not yet recruiting
Facility Name
CHRU de Nancy - Hopitaux de Brabois
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54511
Country
France
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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