Could a lung cancer drug designed for one mutation work for another?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Histologically or cytologically documented non-small cell lung carcinoma 2. Advanced disease defined as recurrent stage IV (according to 8th TNM classification) or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemo-radiation therapy for locally advanced disease) 3. At least one prior platinum-based systemic regimen: Adjuvant or neoadjuvant or definitive platinum-based chemo-radiotherapy treatments are considered as a line of treatment only if completed less than 6 months before enrolment. Maintenance therapy following platinum doublet-based chemotherapy is not considered a separate regimen of therapy. 4. RET rearrangement detected by FISH, Nanostring or by parallel-sequencing on FFPE tumour tissue assessed locally. 5. Availability of FFPE tumour material for central confirmation of RETrearrangement 6. Measurable or non-measurable, but radiologically evaluable (except for skin lesions) disease according to RECIST v1.1 criteria 7. Age ≥18 years 8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 9. Life expectancy \>3 months 10. Adequate haematological function: * Haemoglobin ≥9 g/dL * Neutrophil count ≥1.5 ×109/L * Platelet count ≥100 × 109/L * WBC ≥2 ×109/L 11. Adequate renal function: Calculated creatinine clearance ≥45 mL/min (according to Cockcroft-Gault formula) 12. Adequate liver function: * Total bilirubin ≤2x ULN (except patients with Gilbert Syndrome, who can have total bilirubin ≤3.0 mg/dL) * ALT and AST ≤3x ULN (≤5x ULN for patients with concurrent liver ¨ metastasis) 13. Patient capable of proper therapeutic compliance, and accessible to correct followup. 14. Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine beta HCG pregnancy test within 7 days before enrolment into the trial and within 3 days before alectinib treatment start. 15. Sexually active men and women of childbearing potential must use an effective contraceptive method (intrauterine devices without hormones, bilateral tubal occlusion, vasectomized partner or total abstinence) during the trial treatment and for a period of at least 3 months following the last dose of alectinib. 16. Recovered from any previous therapy related toxicity to Grade ≤1 at date of enrolment (except for recovery to Grade ≤2 of alopecia, fatigue, creatinine increased, lack of appetite or peripheral neuropathy) 17. Written Informed Consent (IC) for trial treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention. Exclusion Criteria: 1. Untreated, active CNS metastases 2. Carcinomatous meningitis 3. Any previous (in the past 3 years) or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast 4. Any serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes, that could affect the patient's capacity to participate in the trial 5. Liver disease characterized by: * ALT or AST \>3 × ULN (\>5 × ULN for patients with concurrent liver metastasis) confirmed on two consecutive measurements or * Impaired excretory function (e.g., hyperbilirubinaemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminaemia, ascites, and bleeding from oesophageal varices or * Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis 6. Patients with baseline symptomatic bradycardia 7. Previous treatment with any RET TKI or RET targeted therapy. 8. Known EGFR, ALK, ROS, and BRAF mutation (in addition to RET rearrangement) 9. Any concurrent systemic anticancer therapy. 10. Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post major bowel resection. 11. History of hypersensitivity to any of the additives in the alectinib drug formulation. 12. Known HIV positivity or AIDS-related illness. 13. Women who are pregnant or in the period of lactation.