Table 1 Key eligibility criteria

1. Histologically confirmed HER2-positive breast cancer;

2. Women and men ≥ 18 years of age;

3. Stage 2–3 breast cancer;

4. No prior therapy for breast cancer;

5. ECOG performance status 0–1;

6. Availability of archival tumour biopsy tissue at screening;

7. Left ventricular ejection fraction (LVEF) ≥ 50%, as determined by ECHO or MUGA

8. Adequate haematologic, hepatic and renal laboratory values (collected ≤ 14 days before registration):

a. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L

b. Platelet count ≥ 100 × 10⁹/L

c. Haemoglobin ≥ 9.0 g/dL

d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN)

e. Total bilirubin ≤ 1.5xULN or < 3 × ULN in the presence of documented Gilbert’s syndrome

f. Serum albumin ≥ 25 g/L

g. Creatinine clearance (CrCL) ≥ 30 ml/min

h. Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN

i. No bloods transfusions or granulocyte-colony stimulating factor within 1 week prior to treatment;

9. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential

1. Known metastatic or stage 4 breast cancer;

2. Unstable angina, new-onset angina (≤ 3 months), myocardial infarction < 6 months before registration, symptomatic congestive heart failure (NYHA class II to IV);

3. Corrected QT interval prolongation to > 470 ms (females) or > 450 ms (males) based on screening 12-lead ECG;

4. Uncontrolled arterial hypertension despite optimal medical management (per investigator’s option);

5. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischaemic attacks), deep venous thrombosis or pulmonary embolism within 3 months before registration;

6. Non-healing wound, ulcer or bone fracture;

7. Active, clinically serious infections > CTCAE grade 2 (CTCAE v5.0) requiring IV antibiotics, antivirals or antifungals;

8. Patients with evidence or history of bleeding diathesis. Any haemorrhage or bleeding event ≥ CTCAE grade 3 within 4 weeks prior to the start of treatment;

9. Active primary immunodeficiency, known HIV, or active hepatitis B or C infection;

10. History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, suspected ILD/pneumonitis that cannot be ruled out by imaging at screening;

11. Lung criteria:

a. Lung-specific intercurrent clinically significant illness, including any underlying pulmonary disorder

b. Any autoimmune, connective tissue or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at time of screening

c. Prior pneumonectomy (complete);

12. Pregnant or breastfeeding female, unwillingness to use contraceptive measures in males and females;

13. Concomitant use of prohibited medications;

14. Known hypersensitivity to the test drug, test drug class, or excipients in the formulation;

15. Any illness or medical condition that is unstable or could jeopardise the safety of patients and their compliance in the study