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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Affibody AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Jun 2025 → ongoing

Decision date (initial)

2025-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Bioequivalence

Part A and Part B: To evaluate safety and tolerability of a single intravenous (IV) infusion of [177Lu]Lu-ABY-271

Secondary objectives 7

1. Part A and Part B: To evaluate dosimetry of [177Lu]Lu-ABY-271
2. Part A and Part B: To evaluate the biodistribution of [177Lu]Lu-ABY-271
3. Part A and Part B: To evaluate the pharmacokinetics (PK) of [177Lu]Lu-ABY-271 in blood and ABY-271 protein levels in plasma
4. Part A and Part B: To evaluate the potential development of anti-drug antibodies (ADAs) against ABY-271 (immunogenicity)
5. Part A only: To determine that [177Lu]Lu-ABY- 271 has an acceptable tumor to normal organ ratio to continue into Part B of the trial
6. Part B only: To evaluate the uptake of [177Lu]LuABY-271 in tumors and in normal tissues using different protein mass doses
7. Part B only: To explore anti-tumor effect

Conditions and MedDRA coding

HER2-positive metastatic breast cancer

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Part A and Part B: Female subject has given her signed declaration of informed consent and data protection declaration
2. Part A and Part B: At least 18 years of age at screening visit
3. Part A and Part B: Subject has unresectable locally advanced or metastatic breast cancer
4. 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
5. Part A and Part B: At least one known tumor lesion ≥ 15 mm
6. Part A and Part B: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
7. Part A and Part B: For females of childbearing potential only: negative serum human chorionic gonadotropin (hCG) test at screening visit
8. 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])
9. Part A and Part B: Willingness and capability of complying with all trial procedure requirements, as per the investigator’s judgement
10. Part A and Part B: Life expectancy of at least 3 months as estimated by the investigator
11. Part A only: Subject is in treatment, or planned to start a new line of standard systemic anti-tumor therapy
12. Part B only: Subject has progressive disease, documented radiologically in the last three months
13. Part B only: Subject has received at least 3 lines of standard systemic anti-tumor therapy in the palliative setting
14. 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

Exclusion criteria 19

1. Part A and Part B: Any organ transplant
2. Part A and Part B: Any known brain metastases
3. 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
4. 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
5. Part A and Part B: Any clinically significant electrocardiogram (ECG) or echocardiogram (ECHO) abnormalities
6. Part A and Part B: Any condition that precludes the proper performance of contrast enhanced computed tomography (ceCT)/ ceMRI scan or SPECT/CT
7. 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
8. 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
9. 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
10. Part A and Part B: History of hypersensitivity or allergy to [177Lu]Lu-ABY-271 or its excipients
11. 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
12. Part A and Part B: Evidence or indication of drug and/or alcohol abuse or dependence, according to the judgment of the investigator
13. Part A only: Previous enrollment in part A of this trial
14. Part B only: Previous enrollment in part B of this trial
15. 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
16. Part A and Part B: Subject is currently pregnant, intending to become pregnant during the course of the trial, or currently breastfeeding
17. 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)
18. 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
19. Part A and Part B: Subject is considered to belong to a vulnerable population (e.g., placed under guardianship, imprisoned)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A and Part B: Treatment emergent adverse events (TEAEs), serious adverse events (SAEs), dose limiting toxicities (DLTs)
2. Part A and Part B: Changes in safety laboratory parameters, vital signs, ECHO, and 12-lead ECG

Secondary endpoints 13

1. Part A and Part B: Absorbed dose in gray (Gy) per organ and selected tumors
2. Part A and Part B: Absorbed dose coefficient (Gy/GBq) per organ and selected tumors
3. Part A and Part B: Normalized whole-body effective dose (millisieverts [mSv]/MBq)
4. Part A and Part B: Time Activity Curves (%ID) for organs and selected tumors
5. Part A and Part B: Plasma concentration of ABY-271 protein after [177Lu]Lu-ABY-271 IV infusion
6. Part A and Part B: Radioactivity concentration in blood of [177Lu]Lu-ABY-271 (kBq/mL)
7. Part A and Part B: Blood PK parameters including tmax, Cmax, Cl, AUC, Vd, MRT, t1/2, λ
8. Part A and Part B: Occurrence of ADAs and change in ADA titers compared to baseline
9. Part A only: Tumor to background absorbed dose ratio for selected organs (e.g., kidney, liver, red marrow)
10. Part A: Tumor to background ratio of activity uptake for selected organs (e.g., kidney, liver, blood)
11. Part B only: Tumor to background absorbed dose ratio for selected organs (e.g., kidney, liver, red marrow)
12. Part B: Tumor to background ratio of activity uptake for selected organs (e.g., kidney, liver, blood)
13. Part B:Objective tumor response as per RECIST v.1.1

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Affibody AB

Sponsor organisation

Affibody AB

Address

Scheeles Vag 2

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Affibody AB

Contact name

Sven Ohlman

Public contact point

Organisation

Affibody AB

Contact name

Anna Uddén

Third parties 3

Locations

2 EU/EEA countries · 6 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 36 files

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

Application history

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