JDQ443 for KRAS G12C NSCLC Brain Metastases

Exclusion Criteria

• •A potential subject who meets any of the following criteria will be excluded from participation in this study:
• •1. Leptomeningeal metastasis (based on MRI or CSF cytology, if strong suspicion despite negative MRI, CSF analysis should be done)
• •2. Previous treatment with KRAS G12C inhibitor except if ≥ 1 year has elapsed since last dose
• •4. History of severe hypersensitivity reaction to JDQ443 or its excipients.
• •5. History of allogeneic bone marrow or solid organ transplant
• •6. Participant has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study treatment or has not recovered from side effects of such procedure.
• •7. Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting the study treatment or participants who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs) radiotherapy ≤ 2 weeks prior to starting the study treatment or has not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study treatment is allowed.
• •8. Clinically significant, uncontrolled cardiac disease and/or recent cardiac events (within 6 months), such as:
• •* Unstable angina or myocardial infarction within 6 months prior to screening.
• •* Symptomatic congestive heart failure (defined as New York Heart Association Grade II or greater).
• •* Documented cardiomyopathy.
• •* Clinically significant cardiac arrhythmias (e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker)
• •* Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, unless controlled prior to first dose of study treatment.
• •* History or current diagnosis of ECG abnormalities indicating significant risk of safety for study participation such as: concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker.
• •* History of familial long QT syndrome or known family history of Torsades de Pointes.
• •* Resting QT interval corrected with Fridericia's formula (QTcF) \> 480 msec on screening ECG or congenital long QT syndrome.
• •* Concomitant medication(s) with a "Known Risk of Torsades de Pointe" per www.qtdrugs.org that cannot be discontinued or replaced by safe alternative
• •9. A medical condition that results in increased photosensitivity (i.e. solar urticaria, lupus erythematosus, etc.).
• •10. History of interstitial lung disease or pneumonitis grade ≥ 2.
• •11. Current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (i.e. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes etc.).
• •12. Malignant disease, other than that is being treated in this study. Exceptions to this criterion include the following: malignancies that were treated curatively and have not recurred within two years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
• •13. Any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment cause unacceptable safety risks, contra-indicate participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, uncontrolled diabetes, hepatic disorders including cirrhosis).
• •14. Any other medical condition (such as active infection including known hepatitis or HIV, treated or untreated), which in the opinion of the Investigator represents an unacceptable risk for participation in the study.
• •15. Any medical condition or prior surgical resection that may affect the absorption of the investigational drug. Examples of medical conditions that may affect investigational drug absorption include (but are not limited to) inflammatory bowel disease (i.e. ulcerative colitis, Crohn's disease) and gastrointestinal disease such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, and malabsorption syndrome.
• •16. Participants who are taking a prohibited medication (strong CYP3A inducers) that cannot be discontinued at least seven days prior to the first dose of study treatment and for the duration of the study.
• •17. Use of any live vaccines against infectious diseases within four weeks of initiation of study treatment.
• •18. Participant is concurrently using other anti-cancer therapy.
• •19. Participation in any additional, parallel, investigational drug or device studies. Participation in non-interventional observational studies which will not influence the endpoints of the current studies is allowed (e.g. liquid biopsies, eNOSE, surveys).
• •20. Pregnant or breast-feeding women or women who plan to become pregnant or breast-feed during the study. Pregnant women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• •21. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 7 days after the last dose of JDQ443.
• •22. Sexually active males unless they use a condom during intercourse while taking study treatment and for 7 days after the last dose of JDQ443. Male participants should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the study treatment via seminal fluid. In addition, male participants must not donate sperm and women participants must not donate oocytes for the time period specified above.