⁃ A. Confirmed diagnosis of a malignancy harbouring HER2 amplification, or an appropriate activating mutation as defined by the MTB, using an analytically validated method.

⁃ • A HER2 amplification copy number between 5-9 will require an MTB discussion. A HER2 amplification copy number ≥10 will be fast-tracked for an MTB recommendation, unless there are any patient-specific individualities that require MTB discussion.

⁃ B. Age 12 years or above.

⁃ C. Women of childbearing potential are eligible provided that they meet the following criteria:

⁃ Have a negative serum or urine pregnancy test before enrolment and;

⁃ Agree to use one form of effective birth control method such as:

⁃ I. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal):

⁃ II. progestogen-only hormonal contraception associated with or without inhibition of ovulation (oral, injectable or implantable)

⁃ III. intrauterine device (IUD)

⁃ IV. intrauterine hormone-releasing system (IUS)

⁃ V. bilateral tubal occlusion

⁃ VI. vasectomised partner

⁃ VII. sexual abstinence

⁃ VIII. male or female condom with or without spermicide

⁃ IX. cap, diaphragm or sponge with spermicide

⁃ Effective from the first administration of trastuzumab or pertuzumab (whichever is first), throughout the trial and for seven months after the last administration of trastuzumab or pertuzumab (whichever is later).

⁃ D. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of trastuzumab or pertuzumab (whichever is first), throughout the trial and for seven months after the last administration of trastuzumab or pertuzumab (whichever is later):

• Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence.

• Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses an effective method of contraception as in C, above.

• Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.

⁃ All male patients must refrain from donating sperm for the same period.

⁃ E. Patients must be able and willing to undergo a fresh tissue biopsy.

⁃ F. ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges shown below. These measurements should be performed to confirm the patient's eligibility.

⁃ Haemoglobin (Hb): ≥90 g/L (transfusion allowed)

⁃ Absolute neutrophil count (ANC): ≥1.5 × 10\^9L (no granulocyte colony-stimulating factor \[GCSF\] support in preceding 72 hours)

⁃ Platelet count: ≥100 × 10\^9L (unsupported for 72 hrs)

⁃ Bilirubin: \<1.5 × upper limit of normal (ULN) Patients with known Gilbert disease: total bilirubin ≤3 × ULN

⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5 × ULN or ≤5 × ULN if raised due to metastases

⁃ Estimated glomerular filtration rate (eGFR): ≥30 mL/min

⁃ Coagulation - prothrombin (PT) (or international normalized ratio \[INR\]) and activated partial thromboplastin clotting time (aPTT): \<1.5 × ULN (unless patient is on anticoagulants, e.g. warfarin \[INR should be stable and within indicated therapeutic range\], or direct oral anticoagulants \[DOAC\])

⁃ G. PAEDIATRIC PATIENTS (\<18 years): Adequate organ function as per haematological and biochemical indices within the ranges shown below. These measurements should be performed to confirm the patient's eligibility.

⁃ Hb: ≥80 g/L (transfusion allowed)

⁃ ANC: \>0.75 × 10\^9/L (no GCSF support in preceding 72 hours)

⁃ Platelet count: ≥75 × 10\^9/L (unsupported for 72 hrs)

⁃ Bilirubin: ≤1.5 × ULN for age

⁃ ALT and AST: ≤2.5 × ULN or ≤5 × ULN if raised due to metastases

⁃ eGFR: ≥60 mL/min (uncorrected value)

⁃ Coagulation - PT (or INR) and aPTT: ≤1.5 × ULN for age (unless patient is on anticoagulants, e.g. warfarin \[INR should be stable and within indicated therapeutic range\], or DOAC).