amg510 (sotorasib) plus lenvatinib as second-line treatment in patients with krasg12c mutant, metastatic nsclc

Conditions: Metastatic Non Small Cell Lung Cancer; KRAS G12C

Summary: amber is a multicentre, single-arm phase ii trial. the protocol treatment consists of of sotorasib plus lenvatinib, as a second-line treatment. the primary objective of the trial is to evaluate the clinical efficacy of sotorasib plus lenvatinib, in terms of objective response rate, for patients with krasg12c-mutant, metastatic nsclc.


Eligibility criteria:
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.

Keywords: metastatic nsclc kras g12c sotorasib lenvatinib