Advanced Breast Cancer, Advanced Gastroesophageal Adenocarcinoma, Advanced Non-small Cell Lung Cancer, Triple-negative Breast Cancer
Conditions
Keywords
Gastroesophageal adenocarcinoma (GEA), Gastric cancer (GC), Breast cancer (BC), Non-small cell lung cancer (NSCLC), Radioligand imaging (RLI), [68Ga]Ga-DWJ155, FKL480, Gallium, Adenocarcinoma, Positron emission tomography (PET), Dosimetry, HER2, Radiopharmaceutical
Brief summary
The purpose of this study is to evaluate the imaging characteristics, safety, biodistribution and pharmacokinetics (PK) of \[68Ga\]Ga-DWJ155, also known as FKL480, in patients ≥ 18 years of age with advanced gastroesophageal adenocarcinoma (aGEA, where GEA is defined as adenocarcinomas of the distal esophagus, the gastroesophageal junction, and the stomach), hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative (HR+/HER2-) advanced breast cancer (aBC), HER2 positive (HER2+) aBC, triple-negative breast cancer (TNBC) and advanced non-small cell lung cancer (aNSCLC) adenocarcinoma.
Detailed description
This is an open-label, Phase I radioligand imaging study designed to assess the biodistribution, imaging, safety, pharmacokinetics (PK), and dosimetry properties of \[68Ga\]Ga-DWJ155. HER2 status for enrollment will be determined based on the most recent, locally available tumor tissue sample and corresponding HER2 results, in accordance with the American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines, as applicable. This study comprises an imaging characterization part and an expansion part. During the imaging characterization part, the imaging characteristics of \[68Ga\]Ga-DWJ155 (e.g., biodistribution, tumor uptake, and radiation dosimetry) will be assessed, as well as the optimal imaging time point for tumor visualization. The expansion part may be initiated if positive tumor uptake is observed in patients during the imaging characterization part. The estimated study duration for each individual patient is up to approximately 32 days, including a screening period of up to 28 days, a single-day imaging period (including \[68Ga\]Ga-DWJ155 administration and assessments), and a 3-day safety follow-up.
Interventions
DIAGNOSTIC_TEST[68Ga]Ga-DWJ155
Radioligand imaging agent
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age ≥ 18 years old * Presence of at least one extracranial measurable lesion by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Patients with one of the following indications: * HR+/HER2- aBC and TNBC: untreated or currently receiving or having completed first line of systemic therapy (preferred); HER2+ aBC: regardless of any prior systemic therapy * aNSCLC adenocarcinoma: Prior to, during or having completed their first line of systemic therapy. If HER2 immunohistochemistry (IHC) will be routinely performed and available, then HER2 ≥1+ * aGEA: regardless of any prior systemic line of therapy Key
Exclusion criteria
* Out-of-range laboratory values defined as: * Estimated glomerular filtration rate (eGFR; calculated using CKD-EPI 2021 formula, or measured) \< 40 mL/min/1.73m2 * Platelet count \< 75 x 10\^9/L * Hemoglobin \< 9 g/dL * Absolute neutrophil count (ANC) \< 1.0 x 10\^9/L * Patients with inadequate hepatic function * Urinary tract obstruction or urinary incontinence * Pregnant or breastfeeding women Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Standardized uptake value ratio (SUVr) of [68Ga]Ga-DWJ155 in tumor lesions relative to reference organs | Up to 180 minutes after the end of injection of [68Ga]Ga-DWJ155 | Standardized uptake value ratios (SUVr) will be calculated as the ratio of SUV in tumor lesions to SUV in normal organs. |
| Standard uptake values (SUVs) of [68Ga]Ga-DWJ155 in selected organs, normal tissue and tumor lesions | Up to 180 minutes after the end of injection of [68Ga]Ga-DWJ155 | Standardized uptake values (SUVs) will be measured in organs of interest, normal tissues, and tumor lesions based on positron emission tomography (PET) imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed concentration (Cmax) of blood radioactivity (Imaging characterization part only) | From pre-dose up to 180 minutes after the end of injection of [68Ga]Ga-DWJ155 | PK analysis will be performed in the imaging characterization part based on decay-corrected blood radioactivity concentration data. These data will be converted to mass units for PK analysis, and Cmax will be determined using non-compartmental methods. |
| Absorbed radiation dose in selected organs and total body (Imaging characterization part only) | Up to 180 minutes after the end of injection of [68Ga]Ga-DWJ155 | Absorbed radiation dose will be estimated for organs of interest and whole body based on serial positron emission tomography (PET) imaging. |
| Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 3 days after the administration of [68Ga]Ga-DWJ155 | Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and echocardiograms (ECGs) qualifying and reported as AEs. |
| Area under the concentration-time curve (AUC) of blood radioactivity (Imaging characterization part only) | From pre-dose up to 180 minutes after the end of injection of [68Ga]Ga-DWJ155 | Pharmacokinetic (PK) analysis will be performed in the imaging characterization part based on decay-corrected blood radioactivity concentration data. These data will be converted to mass units for PK analysis, and AUC will be determined using non-compartmental methods. |
| Effective radiation dose (Imaging characterization part only) | Up to 180 minutes after the end of injection of [68Ga]Ga-DWJ155 | Effective radiation dose will be calculated based on the estimated absorbed radiation doses in source organs, with adjustments for individual body weight and organ masses (derived from computed tomography imaging). |
Countries
Japan
Contacts
CONTACTNovartis Pharmaceuticals
Outcome results
None listed