A multicentre, prospective, open-label study with [68Ga]Ga-ABY-025 PET-imaging to characterize HER2-expression and explore the therapy-predictive value for HER2-antibody drug conjugates in patients with metastatic breast cancer (HER2-Ex PET)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01], Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-12-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Therapy, Efficacy, Safety

To investigate the therapy-predictive role of HER2-PET for the clinical benefit of treatment with T-DXd in patients with HER2-expressing mBC

Secondary objectives 3

1. To assess changes in HER2-status according to [68Ga]Ga-ABY-025 uptake prior to and after 2 cycles of treatment with T-DXd
2. To study the correlation between the proportion of HER2-avid metastases in relation to the total burden of disease (lesions ≥10 mm) on CT, and its prognostic and therapy-predictive value for treatment with T-DXd
3. To study health related quality of life at baseline, the first response evaluation and at disease progression

Conditions and MedDRA coding

Breast Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Female age ≥18 years
2. Metastatic or locally advanced breast cancer with disease progression after ≥ 1 line of chemotherapy in the palliative setting, or with disease relapse within six months after completion of (neo-) adjuvant chemotherapy
3. The patient must be able and willing to provide written consent to participate in the study
4. At least one metastatic lesion ≥ 10 mm is available for biopsy. o Exception can be made when a recent biopsy is available (no more than 12 months old and without exposition to HER2-targeted therapy or local radiotherapy to the specific lesion).
5. At least one additional metastatic index lesion ≥ 10 mm for evaluation of treatment effect (according to RECIST v1.1)
6. WHO performance status ≤ 2
7. Expected survival > 12 weeks
8. Contraceptives: Females of child-bearing potential must agree to use adequate contraception prior to study entry, , for the duration of the study treatment phase and for six months after the last dose of [68Ga]Ga-ABY-025. Examples of 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. Should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. If a female participant is of child-bearing potential (females are considered not of childbearing potential if they are at least one year postmenopausal and/or surgically sterile), she must have a documented negative serum pregnancy test before [68Ga]Ga-ABY-025 administration. Pregnancy testing prior to each administration of the IMP is obligatory.

Exclusion criteria 5

1. Contra-indications for treatment for trastuzumab deruxtecan and inability to undergo this treatment as per local treatment routines
2. A previously documented metastatic tumor biopsy that was HER2-positive (IHC 3+ and/or HER2 gene amplification)
3. Other manifest malignancies except for basal cell carcinoma of the skin
4. Inadequate cardiac, renal, bone marrow or liver function
5. 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 disorders such as haemophilia, von Willebrand disease or platelet disorders or any anticoagulants or antiplatelet treatment that cannot be temporarily paused

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The mean SUVmax in up to five ABY-025 avid lesions at the baseline investigation will be used to assess the primary objective of the study, i.e. to relate HER2-status on PET to the response according to RECIST v1.1 after 3-4 treatment cycles with T-DXd.

Secondary endpoints 3

1. Changes (deltaSUVmax) in HER2-status in up to five target lesions according to [68Ga ]Ga-ABY-025 uptake prior to and after 3-4 cycles of treatment with T-DXd.
2. Correlation between HER2-expressing total tumor volume (HER2-TTV; defined as proportion of ABY-025 avid lesions in relation to the total tumor volume (TTV, lesions ≥10 mm) defined on CT) at baseline and ORR, Progression Free and Overall Survival after treatment with T-DXd
3. Change in patient reported Health-Related Quality of Life (HR-QoL) as measured by the EQ-5D-5L questionnaire from baseline to the first treatment evaluation

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Thuy Tran

Public contact point

Organisation

Karolinska University Hospital

Contact name

Thuy Tran

Third parties 1

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 9 files

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

Application history

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