A First-in-Human phase 1, open-label, two-stage, randomized trial to assess the safety, tolerability, and biodistribution of [177Lu]Lu-ABY-271 in tumors and critical organs in subjects with HER2-positive metastatic breast cancer

Prior treatment

• Part A and Part B: Any organ transplant
• Part A and Part B: Evidence or indication of drug and/or alcohol abuse or dependence, according to the judgment of the investigator
• Part A only: Previous enrollment in part A of this trial
• Part B only: Previous enrollment in part B of this trial
• Part B only: 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

Other illness

• Part A and Part B: History of hypersensitivity or allergy to [177Lu]Lu-ABY-271 or its excipients
• Part A and Part B: Any medical or psychiatric condition which, in the investigator’s opinion, would preclude the subject from adhering to the protocol or completing the clinical trial per protocol
• Part A and Part B: Known history of other malignancy within the last 5 years. Except: malignancies that were treated curatively and have not recurred within 2 years prior to trial treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type
• Part A and Part B: Any condition that precludes the proper performance of contrast enhanced computed tomography (ceCT)/ ceMRI scan or SPECT/CT

Lab values

• Part A and Part B: Any uncontrolled medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject’s safety or interfere with trial participation or interpretation of subject’s results, as assessed by the investigator
• Part A and Part B: Peripheral white blood cells (WBC) <3000/μL with absolute neutrophil count <1500/μL, platelet <100,000/μL or hemoglobin <10 g/dL at screening visit
• Part A and Part B: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN) or total bilirubin levels at ≥1.5 times the ULN at screening visit. Subjects with known Gilbert’s Syndrome who have serum bilirubin <3 x ULN may be enrolled
• Part A and Part B: Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 according to the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation at screening visit

Other

• Part A and Part B: 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
• Part A and Part B: Subject is currently pregnant, intending to become pregnant during the course of the trial, or currently breastfeeding
• Part A and Part B: Subject is an investigator, trial site or Sponsor personnel directly affiliated with this clinical trial and/or their immediate families (partner, spouse, parent, child, or sibling, whether biological or legally adopted)
• Part A and Part B: Subject is considered to belong to a vulnerable population (e.g., placed under guardianship, imprisoned)
• Part A and Part B: Any known brain metastases
• Part A and Part B: Any clinically significant electrocardiogram (ECG) or echocardiogram (ECHO) abnormalities

• Part A and Part B: Female subject has given her signed declaration of informed consent and data protection declaration
• Part A and Part B: Life expectancy of at least 3 months as estimated by the investigator
• 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
• Part B only: Subject has received at least 3 lines of standard systemic anti-tumor therapy in the palliative setting
• Part B only: Subject has received last dose of previous line of systemic anti-tumor therapy, and has no ongoing treatment related toxicities > grade 1 prior to planned first dose of [177Lu]Lu-ABY-271
• Part A and Part B: At least 18 years of age at screening visit
• Part A and Part B: Subject has unresectable locally advanced or metastatic breast cancer
• Part A and Part B: 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
• Part A and Part B: At least one known tumor lesion ≥ 15 mm
• Part A and Part B: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Part A and Part B: For females of childbearing potential only: negative serum human chorionic gonadotropin (hCG) test at screening visit
• Part A and Part B: Willingness and capability of using adequate contraceptive methods from screening visit until 12 weeks after the [177Lu]Lu-ABY-271 dose: a) Female of childbearing potential should use a highly efficient method of contraception (see 8b) but this is not necessary for females of non-childbearing potential who are permanently sterilized or post-menopausal (i.e., at least 12 consecutive months with amenorrhea without other known or suspected medical cause) b) Adequate contraceptive method defined as: i. A method with less than 1% failure rate (e.g., permanent sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner) OR ii. The use of two methods of contraception (e.g., one barrier method [condom, diaphragm, or cervical / vault caps] with spermicide and one hormonal contraceptive [e.g., combined oral contraceptives, patch, vaginal ring, injectables or implants])
• Part A and Part B: Willingness and capability of complying with all trial procedure requirements, as per the investigator’s judgement