MoST addendum 13 (substudy 31): This Phase II trial is evaluating how safe and tolerable a targeted therapy (entrectinib) is in people with newly diagnosed non-squamous non-small cell lung cancer an advanced solid cancers with NTRK fusions or ROS1 gene rearrangementsA single-arm, open-label, phase II trial of the tumour response to entrectinib in patients with advanced tumours harbouring NTRK fusions or ROS1 gene rearrangements detected by comprehensive genomic profiling

Exclusion

1. Prior NTRK and/or ROS1 pathway inhibitor treatment (either approved or investigational)
2. Known history of hypersensitivity or contraindication to entrectinib
3. History of prolonged QTc interval (e.g. repeated demonstration of a QTc interval greater than 450 milliseconds from ECGs performed at least 24 hours apart) or use of medications that are known to prolong the QT interval.
4. History of additional risk factors for torsade de pointes (e.g. family history of long QT syndrome)
5. History of recent (within 3 months prior to screening) symptomatic congestive heart failure or clinically significant cardiac dysfunction, as determined by left ventricular ejection fraction (LVEF) less than 50%
6. Peripheral sensory neuropathy grade greater than or equal to 2
7. Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis
8. Radiation therapy, major surgery, or tumour embolization within 14 days prior to the first dose of entrectinib. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions;
9. Any systemic therapy within 28 days prior to the first dose of entrectinib
10. Administration of any investigational treatment within 28 days prior to receiving the first dose of entrectinib
11. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with entrectinib, including
a. Known active infections that would interfere with the assessment of safety or efficacy of entrectinib (bacterial, fungal, or viral, including HIV positive)
b. Active gastrointestinal disease (e.g. Crohn’s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably affect drug absorption
12. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
13. Any unresolved toxicity (CTCAE v5.0 greater than grade 2) from previous anti-cancer therapy.
14. Prior or concurrent malignancy except for:
a. Malignancy treated with curative intent and with no known active disease within 2 years before consent to molecular screening and of low potential risk for recurrence.
b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
c. Adequately treated carcinoma-in-situ without evidence of disease
15. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or agree to use a highly effective form of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men with partners of childbearing potential must have been surgically sterilised or agree to use a highly effective form of contraception