A First-in-Human Phase 1 Safety and Biodistribution of [177Lu]Lu-ABY-271 in Subjects With HER2-positive Metastatic Breast Cancer

Affibody

Status and phase: Enrolling; Phase 1

Conditions: Metastatic Breast Cancer; HER2 + Breast Cancer

Treatments: Drug: [177Lu]Lu-ABY-271

Study type: Interventional

Funder types: Industry

Identifiers

NCT07081555

Affibody AB

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 4 patient groups

Part A

Experimental group

Description:

\[177Lu\]Lu-ABY-271

Treatment:

Drug: [177Lu]Lu-ABY-271

Part B - Cohort 1

Experimental group

Description:

\[177Lu\]Lu-ABY-271 with protein mass dose A

Treatment:

Drug: [177Lu]Lu-ABY-271

Part B - Cohort 2

Experimental group

Description:

\[177Lu\]Lu-ABY-271 with protein mass dose B

Treatment:

Drug: [177Lu]Lu-ABY-271

Part B - Cohort 3

Experimental group

Description:

\[177Lu\]Lu-ABY-271 with Protein mass dose C

Treatment:

Drug: [177Lu]Lu-ABY-271