MoST Addendum 14 (substudy 32): This phase II study is evaluating the effect of a targeted therapy (alectinib) in people with newly diagnosed metastatic non-squamous small cell lung cancer (NSCLC) or people with advanced solid cancers with ALK gene alterationsA Single arm, open label, phase II trial of tumour response to alectinib in patients with advanced tumours harbouring ALK gene alterations detected by comprehensive genomic profiling

Inclusion

1. Adults, aged 18 years and older, with either:
a. newly diagnosed metastatic non-squamous NSCLC identified through the ASPiRATION molecular screening program OR
b. advanced and/or metastatic solid cancer of any histologic type, refractory or unsuitable for standard therapies for that cancer type, identified through the MoST molecular screening program;
2. Harbouring a targetable ALK gene alteration identified using CGP and determined by the molecular tumour board. NSCLC patients who have an ALK gene alteration determined by IHC must be confirmed by NGS; Pan cancer patients who have ALK overexpression determined by IHC or rearrangement diagnosed by FISH must be confirmed by NGS;
3. NSCLC patients identified through the ASPiRATION molecular screening program must be FISH-negative, i.e. not eligible for PBS-reimbursed ALK-targeted treatment;
4. Confirmation of molecular eligibility by the molecular tumour board;
5. Measurable disease as assessed by RECIST 1.1 and/or RANO;. (Exception: newly diagnosed metastatic, non-squamous NSCLC participants with evaluable but non-measurable disease may be approved on a case-by-case basis by contacting the study chair or delegate through the NHMRC CTC).
6. ECOG 0 to 2;
7. 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; radiation treatment must be completed at least 14 days before enrolment and patients must be clinically stable;
8. 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 100 x 109/L, ANC equal 1.5 x 109/L, and haemoglobin equal 90g/L (5.6mmol/L);
b. liver function; ALT/AST equal 3 x ULN (in the absence of liver metastases, equal 5 x ULN for patients with liver involvement) and total bilirubin equal 1.5xULN;
c. renal function; serum creatinine equal 1.5xULN;
9. Prior anticancer therapy:
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,
iii. Patients previously treated with an ALK inhibitor (other than alectinib) are eligible, unless there is a known on-target resistant mutation (e.g. G1202R) or a compelling off-target resistance mechanism that is deemed unlikely to respond to alectinib, as determined by the MTB. The tumour sample must be obtained from a progression biopsy for genomic screening instead of the archival sample;
10. Life expectancy of at least 12 weeks
11. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
12. Signed, written informed consent to participation in the specific treatment substudy.