[68Ga]Ga-ABY-025 PET in solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Nov 2022 → ongoing

Decision date (initial)

2022-10-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sjöbergstiftelsen · Karolinska University Hospital · Affibody AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To evaluate the HER2 status in lesions (primary tumors and/or metastases) measured by [68Ga]Ga-ABY-025-uptake on PET/CT in patients with GEAC and HER2-low mBC (combined and individual cohorts respectively). The HER2 status defined by IHC-status and ISH-analyses will be used as a reference standard.

Secondary objectives 11

1. 1. To define optimal parameters derived from [68Ga]Ga-ABY-025 PET/CT for separating HER2-positive or HER2-low from HER2-negative disease locations (combined and individual cohorts respectively).
2. 2. To investigate the intra-individual heterogeneity in HER2 status visualized on [68Ga]Ga-ABY-025 PET/CT in lesions determined as metastatic on CT (cohort 1).
3. 3.To investigate whether [68Ga]Ga-ABY-025 PET/CT can visualize tumor lesions with low HER2-expression (HER2-low defined as HER2 1-2+ by IHC).
4. 4. To investigate the added value of whole-body [68Ga]Ga-ABY-025 PET/CT for determination of tumor burden over routine CT (combined and individual cohorts respectively).
5. 5. To assess the safety of the [68Ga]Ga-ABY-025 PET/CT (combined and individual cohorts respectively).
6. Explorative objective 1. To evaluate the changes in HER2 expression determined by [68Ga]Ga-ABY-025-uptake before and early after HER2 targeted treatment (cohort 1).
7. Explorative objective 2. To evaluate the association between HER2 expression determined by [68Ga]Ga-ABY-025-uptake and treatment response (cohort 1).
8. Explorative objective 3. To compare PET/CT with [68Ga]Ga-ABY-025 and with 18F-FDG in the characterization of treatment response of HER2-positive disease locations to HER2 targeted therapies (cohort 1).
9. Explorative objective 4. To investigate whether HER2 expression assessed by [68Ga]Ga-ABY-025-uptake at baseline could be used as a prognostic and therapy-predictive marker (combined and individual cohorts respectively).
10. Explorative objective 5. To investigate myocardial uptake of [68Ga]Ga-ABY-025 as a potential marker for HER2-treatment-induced cardiac toxicity (cohort 1).
11. Explorative objective 6. To investigate the possibility of improved lesion detection and quantification of HER2 expression with kinetic analysis obtained by dynamic PET acquisition compared to static PET images (combined and individual cohorts respectively).

Conditions and MedDRA coding

Gastro-esophageal cancer with HER2-expression (cohort 1). Breast cancer with low HER2-expression (‘HER2-low’) (cohort 2).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Age ≥18 years.
2. 2. The subject has given written consent to participate in the study.
3. 3. 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
4. 4. At least one metastatic lesion ≥ 10 mm is available for biopsy defined on CT.
5. 5. At least one (and up to five) additional metastatic index lesion/s ≥ 10 mm for evaluation of treatment effect
6. 6. WHO performance status ≤ 2.
7. 7. Expected survival > 12 weeks.

Exclusion criteria 9

1. 1. Significantly impaired renal function (GFR <30 ml/min/1.73 m2)
2. 2. Allergy to iodinated contrast media
3. 3. Subjects that for some reason are unable to exercise their rights, such as cognitive function impairment.
4. 4. Other manifest malignancy except for basal cell carcinoma of the skin.
5. 5. 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.
6. 6. 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.
7. 7. 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.
8. 8. 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.
9. 9. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of HER2-expressing lesions (primary tumors and/or metastases) measured by [68Ga]Ga-ABY-025-uptake on PET/CT which are also positive regarding HER2-status defined by reference biopsy-based standard used in clinical routine in patients with GEAC.

Secondary endpoints 11

1. 1. Optimal Standardized Uptake Values (SUVs) and Tumor-to-Background Ratio (TBR) cut-off values for separating HER2-expressing/or HER2-low from HER2-negative lesions by reference standard methods (combined and individual cohorts respectively).
2. 2. Percentage of [68Ga]Ga-ABY-025 uptake sites on whole-body PET/CT compared to all known cancer-related lesions (metastatic and primary, where applicable), determined on the routine radiological investigation with CT as an estimation of intra-individual heterogeneity of HER2-expression (cohort 1).
3. 3. Percentage of false-negative findings on [68Ga]Ga-ABY-025 whole-body PET/CT compared to results from IHC from at least one index lesion in patients with HER2-low mBC (cohort 2, pilot study)
4. 4. Percentage of [68Ga]Ga-ABY-025 uptake in sites, not previously determined on the routine radiological investigation with CT, as a measure of cancer burden determined on the whole body [68Ga]Ga-ABY-025 PET/CT in primary tumors (where applicable) and different metastases (combined and individual cohorts respectively).
5. 5. Frequency of Adverse Events (AEs), Adverse Reactions (ARs), Serious Adverse Events (SAEs), and Suspected Unexpected Serious Adverse Reactions (SUSARs) (combined and individual cohorts respectively).
6. Exploratory endpoint 1. To examine the change in HER2 expression measured by [68Ga]Ga-ABY-025-uptake on PET/CT (SUVs and TBR) performed after 3 courses of chemotherapy/HER2 targeted drugs compared to pre-treatment values and in which proportion of the examined patients this occur (cohort 1).
7. Exploratory endpoint 2. Changes in SUVs in index lesions, as well as in the total HER2-expressing tumor volume at [68Ga]Ga-ABY-025 PET/CT (percentage) before and after treatment with systemic therapy including HER2 targeted drugs to evaluate treatment response (cohort 1).
8. Exploratory endpoint 3. Comparison of treatment response evaluation performed by [68Ga]Ga-ABY-025 PET/CT versus 18F-FDG PET/CT defined as percentage of complete and partial response, stable and progressive disease (percentage of concordant results, cohort 1).
9. Exploratory endpoint 4. The correlation between HER2 expression measured by a total HER2-expressing tumor volume at [68Ga]Ga-ABY-025 PET before treatment and progression-free survival (PFS), overall (or clinical) response rate to systemic therapy (ORR) at 12 months after inclusion (combined and individual cohorts respectively).
10. Exploratory endpoint 5. The presence and frequency of myocardial uptake of [68Ga]Ga-ABY-025 and relation to treatment-related cardiotoxicity by echocardiography (cohort 1).
11. Exploratory endpoint 6. The agreement between WB imaging and kinetic parameters in the determination of HER2-status (combined and individual cohorts respectively).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Halsovagen, Flemingsberg Flemingsberg

City

Huddinge

Postcode

141 86

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Rimma Axelsson

Public contact point

Organisation

Karolinska University Hospital

Contact name

Rimma Axelsson

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications