Phase II study of [68Ga]Ga-ABY-025 PET for non-invasive quantification of HER2-status in solid tumors.
- Trial ID
- 2022-500448-39-00
- Protocol
- K2020-9716
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase II study is to evaluate the **HER2 status** in lesions, including primary tumors and/or metastases, using [68Ga]Ga-ABY-025 uptake on PET/CT in patients with gastro-esophageal cancer and HER2-low metastatic breast cancer. The HER2 status determined by immunohistochemistry (IHC) and in situ hybridization (ISH) analyses will serve as the reference standard. This evaluation is clinically relevant as it aims to provide a non-invasive method for quantifying HER2 expression, which is crucial for guiding targeted therapies in these cancer types.
Secondary objectives include:
- Defining optimal parameters from [68Ga]Ga-ABY-025 PET/CT for distinguishing HER2-positive or HER2-low from HER2-negative disease locations.
- Investigating intra-individual heterogeneity in HER2 status visualized on [68Ga]Ga-ABY-025 PET/CT in metastatic lesions.
- Assessing the ability of [68Ga]Ga-ABY-025 PET/CT to visualize tumor lesions with low HER2 expression.
- Evaluating the added value of whole-body [68Ga]Ga-ABY-025 PET/CT for determining tumor burden compared to routine CT.
- Assessing the safety of [68Ga]Ga-ABY-025 PET/CT.
- Exploring changes in HER2 expression before and after HER2-targeted treatment, the association between HER2 expression and treatment response, and comparing PET/CT with [68Ga]Ga-ABY-025 and 18F-FDG in characterizing treatment response.
- Investigating HER2 expression as a prognostic and therapy-predictive marker, myocardial uptake as a marker for cardiac toxicity, and the potential for improved lesion detection and quantification with kinetic analysis.
Participants
The clinical trial involves participants diagnosed with **gastro-esophageal cancer** with HER2-expression and breast cancer with low HER2-expression. The study population includes both male and female subjects aged 18 years and older, with no vulnerable populations selected. Participants are required to have metastatic disease due to gastroesophageal adenocarcinoma, non-small cell lung cancer, or HER2-low metastatic breast cancer. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants must have at least one metastatic lesion of 10 mm or greater available for biopsy, and a WHO performance status of 2 or less. The expected survival of participants is greater than 12 weeks. The trial population was selected based on these criteria, ensuring that individuals are suitable for the evaluation of HER2 status using PET/CT imaging. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data.
Plans and Procedures
The clinical trial is designed as a **Phase II** study to evaluate the **HER2 status** in lesions of patients with gastro-esophageal cancer and breast cancer with low HER2 expression. The trial employs a **randomized, double-blind, controlled** methodology to ensure the reliability and validity of the results. The study is expected to run from November 2022 to December 2025, with participant involvement lasting up to two years, depending on individual treatment responses and conditions.
Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age, written consent, and the presence of metastatic disease. The inclusion visit will also involve a baseline assessment of **HER2 status** using PET/CT imaging with **[68Ga]Ga-ABY-025**. Follow-up visits will occur at regular intervals to monitor the uptake of the investigational product and assess treatment effects. These visits will include imaging assessments and evaluations of any adverse events. The end-of-study visit will conclude the participant's involvement, with a final assessment of **HER2 expression** and overall treatment response.
Participants are expected to remain in the study for its full duration unless specific conditions necessitate early termination. Such conditions include significant adverse reactions, withdrawal of consent, or progression of disease beyond predefined criteria. The primary endpoint of the study is the percentage of **HER2-expressing lesions** identified by PET/CT that correlate with biopsy-based standards. Secondary endpoints include the determination of optimal uptake values and the frequency of adverse events. The study aims to provide valuable insights into the non-invasive quantification of **HER2 status** in solid tumors, potentially influencing future therapeutic strategies.
Treatment
The clinical trial involves the administration of the experimental medication **Gallium (68Ga) Tezatabep Matraxetan**, which is provided in the form of a **solution for injection**. This investigational product is identified by the sponsor product code **68Ga-ABY-025** and is manufactured by Affibody AB. The pharmaceutical form is a solution specifically designed for intravenous administration. The dosing regimen for this trial specifies a maximum daily dose of 220.00 MBq (megabecquerels) and a maximum total dose of 440.00 MBq over a treatment period of up to 2 days. The administration of the drug is conducted intravenously, ensuring direct delivery into the bloodstream for optimal uptake and imaging purposes.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the investigational product, **Gallium (68Ga) Tezatabep Matraxetan**, to evaluate its efficacy in non-invasive quantification of HER2-status in solid tumors using PET/CT imaging. Participant compliance with the dosing schedule is monitored through standard clinical trial procedures to ensure adherence to the protocol and accurate assessment of the investigational product's effects.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the **HER2** status in lesions, including primary tumors and metastases, using [68Ga]Ga-ABY-025 uptake on PET/CT scans. The primary endpoint is the percentage of HER2-expressing lesions that are also positive for HER2 status as defined by a reference biopsy-based standard used in clinical routine for patients with gastroesophageal adenocarcinoma (GEAC). Secondary endpoints include determining optimal Standardized Uptake Values (SUVs) and Tumor-to-Background Ratio (TBR) cut-off values for distinguishing HER2-expressing or HER2-low from HER2-negative lesions, as well as assessing the percentage of [68Ga]Ga-ABY-025 uptake sites on whole-body PET/CT compared to all known cancer-related lesions. Additional secondary endpoints involve evaluating the percentage of false-negative findings on [68Ga]Ga-ABY-025 whole-body PET/CT compared to immunohistochemistry (IHC) results, and the percentage of [68Ga]Ga-ABY-025 uptake in sites not previously identified on routine CT scans.
Exploratory endpoints will examine changes in HER2 expression measured by [68Ga]Ga-ABY-025 uptake on PET/CT after chemotherapy or HER2-targeted drug courses, and the correlation between HER2 expression and progression-free survival (PFS) or overall response rate (ORR) at 12 months post-inclusion. The trial will also explore the presence and frequency of myocardial uptake of [68Ga]Ga-ABY-025 and its relation to treatment-related cardiotoxicity. Efficacy assessments will be conducted using PET/CT imaging, with data collected at specified timepoints to evaluate treatment response and intra-individual heterogeneity of HER2 expression. The trial is designed to provide comprehensive insights into the efficacy of [68Ga]Ga-ABY-025 PET/CT in non-invasively quantifying HER2 status in solid tumors.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥18 years.
- The subject has given written consent to participate in the study.
- Patients with metastatic disease because of gastroesophageal adenocarcinoma, NSCLC or HER2-low breast cancer. Cohort 1: Histologically confirmed HER2-positive primary gastroesophageal adenocarcinoma, scheduled for palliative HER2-targeted therapy; Cohort 2: HER2-positive status in non-small cell lung cancer, scheduled for palliative HER2-targeted therapy; Cohort 3: HER2-low metastatic breast cancer first within a pilot study (of which five patients with de novo HER2-low mBC and five patients with pre-treated HER2-low mBC). Later, within a post-pilot study. For definition of HER2 status in each cohort see Supplement 16.b
- At least one metastatic lesion ≥ 10 mm is available for biopsy defined on CT.
- At least one (and up to five) additional metastatic index lesion/s ≥ 10 mm for evaluation of treatment effect
- WHO performance status ≤ 2.
- Expected survival > 12 weeks.
Exclusion Criteria
- Significantly impaired renal function (GFR <30 ml/min/1.73 m2)
- Allergy to iodinated contrast media
- Subjects that for some reason are unable to exercise their rights, such as cognitive function impairment.
- Other manifest malignancy except for basal cell carcinoma of the skin.
- The patient presenting any contraindication for the use of HER2 targeted therapy for metastatic disease: congestive heart failure, baseline left ventricular ejection fraction (LVEF) less than 50%, transmural myocardial infarction, uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg), angina pectoris requiring medication, clinically significant valvular heart disease, high-risk arrhythmias, lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome, active gastrointestinal bleeding.
- Inadequate organ function, suggested by the following laboratory results: absolute neutrophil count <1,500 cells/mm3, haemoglobin <90 g/L, total bilirubin ≥1.5 x ULN (unless the patient has documented Gilbert’s syndrome), AST (SGOT) or ALT (SGPT) >5.0 x ULN.
- Positive pregnancy test in women of childbearing potential (premenopausal or <12 months of amenorrhea post-menopause and who have not undergone surgical sterilization) or lactation.
- Female patients of childbearing potential and sexually active and not willing to use a highly effective contraceptive. Examples of highly effective contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Women must refrain from donating eggs during this same period.
- Patients with increased risk of complications from biopsies, i.e. increased risk of bleeding, defined as - prothrombin time test (INR value) >1.4, platelet count <70 (109/l), activated partial thromboplastin time (APTT) >30s. - known bleeding disorder such as hemophilia, von Willebrand disease or platelet disorders. - any anticoagulants or antiplatelet treatment (except for low-dose ASA, i. e 75 mg daily).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Sweden | Not Recruiting | 11 Nov 2022 | 72 |