MoST Addendum 8: This Phase II study is trying to understand how effective a targeted therapy (trastuzumab emtansine) is in people with cancers with HER2 amplifications or mutationsSingle arm, open label, signal seeking, phase IIa trial of the activity of Trastuzumab emtansine (T-DM1) in patients with tumours harbouring HER2 amplifications or mutations

Inclusion

 Male or female participants, aged 18 years and older, with either
a. advanced and/or metastatic solid cancer of any histologic type, refractory or unsuitable for standard therapies for that cancer type; or
b. newly diagnosed metastatic, non-squamous NSCLC
2. Patients with tumours harbouring HER2 mutations or amplification (in the absence of a mutation) identified using comprehensive genomic profiling (CGP) and determined by the molecular tumour board. (Exception: ASPiRATION participants with HER2 mutation with/without amplification are eligible).
3. Confirmation of molecular eligibility by the molecular tumour board
4. Measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and/or RANO. (Exception: ASPiRATION participants with evaluable but non-measurable disease may be approved on a case-by-case basis by contacting the ASPiRATION study chair or delegate through the NHMRC CTC).
5. ECOG 0-2
6. If the CNS is involved (either primary or metastatic disease), this must be asymptomatic or previously treated and controlled either with local treatment or by steroids
7. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug):
a. bone marrow function; platelets equal or more than 100 x 10^9/L, ANC equal or more than 1.5 x 10^9/L, and haemoglobin equal or more than 9g/dL (5.6mmol/L);
b. liver function; ALT/AST equal or less than 2.5 x ULN and total bilirubin equal or less than 1.5xULN;
c. renal function: creatinine clearance greater than 50 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR) estimation: (140 - Age) × (weight in kg) × (0.85 if female)/(72 × serum creatinine);
8. Prior anticancer therapy (excluding HER2 inhibitors)
a. For newly diagnosed metastatic, non-squamous NSCLC:
i. Up to 2 cycles of systemic therapy while awaiting the results of CGP testing are permitted (but not required);
b. For advanced and/or metastatic treatment-refractory solid cancer of any histologic type:
i. Participants must have received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists.
ii. Clinical or radiological progression on, or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance
9. ALP equal or less than 2.5 ×ULN with the following exception: patients with bone metastases: ALP equal of less than 5 ×ULN
10. INR and aPTT less then 1.5 x ULN (unless on therapeutic coagulation)
11. Albumin equal or more than 25mg/dL
12. Life expectancy greater than or equal to 12 weeks