OSIBOOST 2

Using Cobicistat as a pharmacokinetic booster of Osimertinib and implementing alternative dose-regimens to improve cost effectiveness of advanced NSCLC treatment: OSIBOOST 2-A and OSIBOOST 2-B

In order to be eligible to participate in this OSIBOOST 2-A, a participant must meet all of the following criteria:
+ The patient receives osimertinib 80 mg QD as part of their standard treatment plan.
+ The patient has a World Health Organization (WHO) Performance Status (PS) of 0-2.
+ The patient is 18 years or older.
+ The patient is able and willing to sign informed consent.
+ The patient is able and willing to undergo additional blood sampling for e.g. TDM.
+ The patient has non-squamous advanced EGFR-mutated NSCLC with CT confirmed stable disease or better. Patients with (signs of) progression, are also eligible if their treating physician deems the treatment to be appropriate beyond progression, with an expected treatment duration with osimertinib of at least 12 weeks after enrolment in OSIBOOST 2A.
+ The patient consents to their blood being analysed for CYP3A-genotype.
The patient is willing to use adequate contraception.
In order to be eligible to participate in OSIBOOST 2-B, a participant must meet all of the following criteria:
+ The patient is receives osimertinib 80 mg QD as part of their standard treatment plan.
+ The patient has a World Health Organization (WHO) Performance Status (PS) of 0-2.
+ The patient is 18 years or older.
+ The patient is able and willing to sign informed consent.
+ The patient is able and willing to undergo additional blood sampling for e.g. TDM.
+ The patient has non-squamous EGFR-mutated NSCLC with radiologically confirmed progressive (RANO-BM/RANO-LM), but asymptomatic intracranial metastasis, not in an eloquent area (to be discussed with neurologist). Furthermore, the disease is either controlled extracranially (stable disease or better), or the treating physician deems the treatment to be appropriate to be continued beyond progression, with an expected treatment duration with osimertinib of at least 12 weeks after enrolment in OSIBOOST 2B.
The patient is willing to use adequate contraception.

A potential participant who meets any of the following criteria will be excluded from participation in this study:
– The patient is taking any other drug which is known to strongly inhibit CYP3A4/CYP3A5, P-gp or BCRP activity (as described in 8.1.2).
– The patient is taking any other drug which is primarily metabolized by CYP3A4/CYP3A5, P-GP or BCRP and which has a small therapeutic window (as described in 8.1.2).
– The patient is taking any drug or (food or herb, such as St. John’s Wort) product which may otherwise affect CYP3A4/CYP3A5, P-gp or BCRP metabolic activity (as described in 8.1.2).
– The patient has impaired gastrointestinal function that may alter the absorption of osimertinib or cobicistat (e.g. ulcerative disease, uncontrolled nausea or vomiting, malabsorption syndrome, small bowel resection).
– The patient has Child-Pugh score class C or chronic liver disease.
– The patient has any condition which is contra-indicated for treatment with osimertinib (e.g. hypersensitivity to the active substance (osimertinib (as mesylate)) or to any of the excipients and/or QTc-prolongation (i.e. QTc interval greater than 481 msec on at least 2 separate electrocardiograms (ECGs)).
– The patient is either pregnant, breastfeeding, or actively trying to conceive.