HER2 + Breast Cancer, Metastatic Breast Cancer
Conditions
Keywords
Radiopharmaceutical, Biodistribution, First-in-human, phase 1, safety
Brief summary
This is a FiH phase 1, open-label, two-stage, randomized trial to assess the safety, tolerability, and biodistribution of \[177Lu\]Lu-ABY-271 in subjects with HER2 positive metastatic breast cancer.
Detailed description
The trial consists of two parts: Part A in which the uptake of \[177Lu\]Lu-ABY-271 in tumors and critical organs will be evaluated and up to 6 subjects will be enrolled sequentially. Part B in which the optimal protein mass dose range (mg) to be utilized in subsequent clinical trials will be evaluated. 15 subjects will be randomized to 3 different protein mass dose levels (1:1:1), divided into two sequential cohorts with different radioactivity levels.
Interventions
DRUG[177Lu]Lu-ABY-271
A single infusion of \[177Lu\]Lu-ABY-271
Sponsors
Affibody
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The trial consists of two parts: Part A in which up to 6 subjects will be enrolled sequentially. Part B in which 15 subjects will be randomized to 3 different protein mass dose levels (1:1:1), divided into two sequential cohorts
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has unresectable locally advanced or metastatic breast cancer * Subject with histologically or cytologically confirmed carcinoma with documented HER2 overexpression (biopsy not older than 2 years): immunohistochemistry (IHC) score 3+; OR 2+ and fluorescence in situ hybridization (ISH) positive * At least one known tumor lesion ≥ 15 mm * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Part A only \- Subject is in treatment, or planned to start a new line of standard systemic anti-tumor therapy Part B only * Subject has progressive disease, documented radiologically in the last three months * Subject has received at least 3 lines of standard systemic anti-tumor therapy in the palliative setting * Subject has received last dose of previous line of systemic anti-tumor therapy, and has no ongoing treatment related toxicities \> grade 1 (except alopecia) prior to planned first dose of \[177Lu\]Lu-ABY-271
Exclusion criteria
* Active brain metastases * Administration of another IMP within 5 half-lives (for experimental biologics: 6 months or 5 half-lives, whichever is longer) of the planned first dose of \[177Lu\]Lu-ABY-271 * Exposure to any anti-tumor therapy since the last documented progression, including any radiotherapy within 7 days prior to the planned first dose of \[177Lu\]Lu-ABY-271
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment emergent adverse events | From baseline to the end-of-trial visit, for part A Day 29 and for part B Day 43 |
| Dose Limiting Toxicities | From baseline to the end-of-trial visit, for part A Day 29 and for part B Day 43 |
Secondary
| Measure | Time frame |
|---|---|
| Absorbed dose in gray (Gy) per organ and selected tumors | From baseline to day 8 |
| Absorbed dose coefficient (Gy/GBq) per organ and selected tumors | From baseline to day 8 |
| Normalized whole-body effective dose (millisieverts [mSv]/MBq) | From baseline to day 8 |
Countries
Sweden
Contacts
Primary ContactAffibody AB
Outcome results
None listed