SHERLOCK: Phase 2 trial of sotorasib in combination with carboplatin-pemetrexed and bevacizumab-biosimilar as first line treatment for advanced non-squamous non-small cell lung cancer with KRAS G12C mutation

Exclusion Criteria24

• Previous treatment with sotorasib, or KRAS G12C specific inhibitor, or pan-KRAS inhibitor
• Concurrent driver mutation (including EGFR, ALK, ROS1, BRAF) where an approved targeted therapy is available
• Mixed histology with any small cell or squamous component
• Evidence of active bleeding or bleeding risk, including:
• a tumour that compresses or invades major blood vessels or tumour cavitation that in the opinion of the investigator is likely to bleed
• History of haemoptysis (>2.5 mL per event) in the last 3 months or severe bleeding
• Bleeding disorders, haemorrhagic diathesis
• Chronic systemic anticoagulation with aspirin > 100 mg/day, clopidogrel > 75 mg/day, ticagrelor > 90 mg BD, more than one anti-platelet drug, warfarin, heparin, enoxaparin, and other direct oral anticoagulants (e.g. apixaban, rivaroxaban, etc)
• Medically uncontrolled hypertension or systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg. If “white coat” hypertension is suspected, a 24-hour continuous blood pressure recording is required to accurately determine blood pressure.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to registration, unstable arrhythmias, or unstable angina
• Significant peripheral vascular disease or cerebrovascular disease (including stroke or transient ischaemic attack within 6 months prior to registration)
• Concurrent medical illness that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
• Severe infection within 4 weeks prior to registration including, but not limited to hospitalisation for management of infection, bacteraemia or sepsis.
• Active hepatitis B, hepatitis C, or HIV. Chronic hepatitis B carrier with undetectable hepatitis DNA level is allowed. Serological testing is not mandatory unless clinically indicated.
• Major surgery within 28 days prior to registration
• Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to swallow oral tablet medication
• History of a malignancy within 5 years prior to registration except for non-melanomatous carcinoma of the skin
• Spinal cord compression, symptomatic and unstable brain metastases, except for those participants who have completed definitive therapy, are not on steroids equivalent to oral prednisone of > 10 mg/day, and have a stable neurological status for at least 2 weeks after commencement of the definitive therapy. Participants with untreated asymptomatic brain metastases can be eligible for inclusion if immediate definitive treatment is not indicated
• Leptomeningeal disease
• Known allergy or hypersensitivity to any of the study drugs or their excipients
• Life expectancy of less than 3 months
• Current enrolment or participation in another clinical study with an unregistered investigational product during the last 12 months, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study, in which case eligibility should be discussed with the Study Chair by contacting the NHMRC CTC.
• Serious medical or psychiatric conditions that might limit the ability of the participant to comply with the protocol.
• Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception