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
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A: [68Ga]Ga-DPI-4452 Participants will receive [68Ga]Ga-DPI-4452, a single dose on Day 1. |
Drug: [68Ga]Ga-DPI-4452
[68Ga]Ga-DPI-4452, administered as IV injection.
|
| 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. |
Drug: [68Ga]Ga-DPI-4452
[68Ga]Ga-DPI-4452, administered as IV injection.
Drug: [177Lu]Lu-DPI-4452
[177Lu]Lu-DPI-4452, administered as IV infusion.
|
| 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. |
Drug: [68Ga]Ga-DPI-4452
[68Ga]Ga-DPI-4452, administered as IV injection.
Drug: [177Lu]Lu-DPI-4452
[177Lu]Lu-DPI-4452, administered as IV infusion.
|
Outcome Measures
Primary Outcome Measures
- 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 (28 days)]
- Part C: Objective Response Rate (ORR) [Up to approximately 2 years]
Secondary Outcome Measures
- Part A: Concentration of [68Ga]Ga-DPI-4452 in Blood [Pre-dose and at multiple time points 6 hours post-dose on Day 1]
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 [Day 1]
- Part B: Objective Response Rate (ORR) [Up to approximately 2 years]
- Parts B and C: Concentration of [177Lu]Lu-DPI-4452 in Blood and Plasma [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}]
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 [6 months]
- Parts B and C: Progression Free Survival (PFS) [Up to approximately 2 years]
- Parts B and C: Overall Survival (OS) [Up to approximately 2 years]
- Parts B and C: Duration of Response (DoR) [Up to approximately 2 years]
- Parts B and C: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Up to approximately 2 years]
- 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 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)]
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 [Part A: Day 1; Part B and C: Baseline]
- Parts B and C: Disease Control Rate (DCR) [Up to approximately 2 years]
- Parts A, B and C: Human Dosimetry [68Ga]Ga-DPI-4452 [Part A: Day 1; Parts B and C: Cycle 1 (each cycle= 28 days)]
Whole body effective dose will be calculated using the PET scan.
Eligibility Criteria
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 confirmed, unresectable locally advanced or metastatic clear cell renal cell cancer (ccRCC), pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer, (CRC).
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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).
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Presence of at least 1 non-irradiated tumor lesion detected at conventional imaging (CT/MRI) documented within 4 weeks prior to the [68Ga]Ga-DPI-4452 administration.
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Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1
Exclusion Criteria:
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Any major surgery within 12 weeks before enrollment
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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:
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Has known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
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Bladder outflow obstruction or unmanageable urinary incontinence.
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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]).
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Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of [68Ga]Ga-DPI-4452.
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Previous Carbonic anhydrase (CA) IX-targeting treatment.
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Prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow, as judged by the Investigator.
Part B and Part C:
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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.
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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).
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Administration of a radiopharmaceutical with therapeutic intent within a period of 6 months prior to injection of [68Ga]Ga-DPI-4452.
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Any previous CA IX-targeting treatment for more than 1 cycle or 1 month.
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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).
Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Debiopharm International SA
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Debio 0228-101
- 2022-002573-28