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

Colorectal Cancer (CRC) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05706129
• Other study ID #: Debio 0228-101
• Secondary ID: 2022-002573-2820
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 14, 2023
• Est. completion date: January 2027

Study information

• Verified date: March 2024
• Source: Debiopharm International SA
• Contact: Debiopharm International S.A
• Phone: +41 21 321 01 11
• Email: clinicaltrials[@]debiopharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: January 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Colorectal Cancer (CRC)
• Pancreatic Ductal Adenocarcinoma (PDAC)

Intervention

Drug:
• [68Ga]Ga-DPI-4452
[68Ga]Ga-DPI-4452, administered as IV injection.
• [177Lu]Lu-DPI-4452
[177Lu]Lu-DPI-4452, administered as IV infusion.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	UNSW Sydney, St Vincent's Hospital Sydney	Sydney
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Léon Bérard	Lyon Cedex
France	AP-HM - Hopital de la Timone	Marseille
France	CHU de Nantes	Nantes
France	IUCT - Oncopole	Toulouse
France	CHRU de Nancy - Hopitaux de Brabois	Vandœuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

Australia,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Up to Day 7
Primary	Part B: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)		Cycle 1 (28 days)
Primary	Part C: Objective Response Rate (ORR)		Up to approximately 2 years
Secondary	Part A: Concentration of [68Ga]Ga-DPI-4452 in Blood	Pharmacokinetics (PK) will be evaluated in blood for radioactivity of [68Ga]Ga-DPI-4452.	Pre-dose and at multiple time points up to 4 hours post-dose on Day 1
Secondary	Part A: Radioligand [68Ga]Ga-DPI-4452 Positron Emission Tomography (PET) Scan Time-Window for Optimal Imaging		Day 1
Secondary	Part B: Objective Response Rate (ORR)		Up to approximately 2 years
Secondary	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.	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	Parts B and C: Progression Free Survival (PFS) Rate at 6 Months		6 months
Secondary	Parts B and C: Progression Free Survival (PFS)		Up to approximately 2 years
Secondary	Parts B and C: Overall Survival (OS)		Up to approximately 2 years
Secondary	Parts B and C: Duration of Response (DoR)		Up to approximately 2 years
Secondary	Parts B and C: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Up to approximately 2 years
Secondary	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.	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	Parts A, B and C: Number of Positive Tumor Lesions Detected by Imaging		Part A: Day 1; Part B and C: Baseline
Secondary	Parts B and C: Disease Control Rate (DCR)		Up to approximately 2 years
Secondary	Parts A, B and C: Human Dosimetry [68Ga]Ga-DPI-4452	Whole body effective dose will be calculated using the PET scan.	Part A: Day 1; Parts B and C: Cycle 1 (each cycle= 28 days)