AMG510 (sotorasib) Plus Lenvatinib As Second-line Treatment in Patients with KRASG12C Mutant, Metastatic NSCLC

Inclusion Criteria: * Pathologically documented metastatic NSCLC. * Documented disease progression on prior treatment. Prior treatment must have included platinum-based doublet chemotherapy and immune-checkpoint inhibition. * KRASG12C-mutation (identified through local molecular testing, using a validated test). * Measurable disease per RECIST v1.1 criteria. * Age ≥18 years. * ECOG Performance Status of 0-1. * Life expectancy of \>3 months. * Ability to swallow oral medications and willing to complete a treatment diary. * Adequate haematological function. * Adequate renal function. * Adequate liver function. * Men and women of childbearing potential must use highly effective contraception. * Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 5 weeks before enrolment. Pregnancy test must be repeated within 3 days before the first dose of protocol treatment. * Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention. Exclusion Criteria: * Active brain metastases E.g., untreated brain lesions (new or progressing) and/or symptomatic brain lesions (symptoms as determined by the investigator). Patients who have had brain metastases resected or have received whole brain radiation therapy ending at least 4 weeks (or stereotactic radiosurgery ending at least 2 weeks) prior to enrolment are eligible if they meet all of the following criteria: * Residual neurological symptoms are only of grade ≤2 * On stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable. * History or presence of haematological malignancies. Exception: curatively treated haematological malignancies with no disease evidence in the last 2 years. * History of (non-infectious) pneumonitis that required steroids or evidence of ILD/pneumonitis. * Active hepatitis B and C and uncontrolled HIV. * Uncontrolled blood pressure (systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg) in spite of an optimised regimen of antihypertensive medication. * Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, long QT syndrome (LQTS), unstable angina, myocardial infarction or stroke within 6 months before enrolment, or cardiac arrhythmia requiring medical treatment at screening * Bleeding or thrombotic disorders or patients at risk for severe haemorrhage. The degree of tumour invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe haemorrhage associated with tumour shrinkage/necrosis following lenvatinib therapy. * Current or recent (within 10 days of enrolment) use of aspirin (\>325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, or clostazol. * Electrolyte abnormalities that have not been corrected. * Proteinuria on urine dipstick testing \>1+, unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \<2 g/24 hours. * History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to inclusion. * Unresolved toxicities from previous lines of anti-cancer treatment regimens and/or (with the exception of alopecia) complications from major surgery prior to enrolment. * Previous treatment with KRAS- and/or VEGF/R inhibitors. * Hypersensitivity to sotorasib or lenvatinib. * Women who are pregnant or breastfeeding or who are planning to become pregnant or breastfeed. * Sexually active men and women of childbearing potential who are not willing to use a highly effective contraceptive method during the trial and for 7 days after the last dose of sotorasib and until 30 days after the last dose of lenvatinib. * Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.