COBICISTAT for Non-small cell lung cancer (EGFR-mutated)

Inclusion criteria

• {"criterion_text":"- The patient receives osimertinib 80 mg once daily as part of their standard treatment plan."}
• {"criterion_text":"- The patient has a World Health Organisation (WHO) Performance Status (PS) of 0-2."}
• {"criterion_text":"- The patient is 18 years or older."}
• {"criterion_text":"- The patient is able and willing to sign informed consent."}
• {"criterion_text":"- The patient is able and willing to undergo additional blood sampling (e.g. for therapeutic drug monitoring)."}
• {"criterion_text":"- The patient consents to their blood being analysed for CYP3A-genotype."}
• {"criterion_text":"- OSIBOOST 2-A: the patient has non-squamous advanced EGFR-mutated NSCLC with no signs of imminent progression (CT-confirmed). If the patient does have signs of progression, they are only eligible if their treating physician deems treatment beyond progression to be appropriate."}
• {"criterion_text":"- OSIBOOST 2-B: the patient has non-squamous EGFR-mutated NSCLC with radiologically confirmed (RANO-progressive) asymptomatic intracranial progression, not in an eloquent area. Furthermore, extracranial disease should be controlled (no RECIST v1.1 progression)."}

Exclusion criteria

• {"criterion_text":"- The patient is taking any other drug or herbal substance which 1) is known to strongly inhibit CYP3A, P-gp or BCRP activity; 2) is primarily metabolized by CYP3A, P-gp or BCRP and has a small therapeutic range; or 3) may otherwise affect CYP3A, P-gp or BCRP metabolic activity."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- The patient has chronic liver disease (Child-Pugh score: class C)."}
• {"criterion_text":"- The patient is either pregnant or breastfeeding."}

Primary endpoints

• {"endpoint_text":"- OSIBOOST 2-A: The daily cumulative dose reduction accomplished in individual patients, while retaining osimertinib exposure (i.e. osimertinib trough (Cmin,SS) levels within the specified provisional therapeutic range (125 – 259 ng/mL).","definition_or_measurement_approach":"Measured as individual patient cumulative dose reduction while maintaining osimertinib trough (Cmin,SS) concentrations within the provisional therapeutic window 125–259 ng/mL (therapeutic drug monitoring of trough levels)."}
• {"endpoint_text":"- OSIBOOST 2-B: CNS disease control rate (DCR) at 12 weeks.","definition_or_measurement_approach":"CNS disease control rate assessed at 12 weeks (DCR at 12 weeks)."}

Secondary endpoints

• {"endpoint_text":"- Osimertinib and AZ5104 trough concentrations in plasma during steady state","definition_or_measurement_approach":"Trough plasma concentrations of osimertinib and its active metabolite AZ5104 at steady-state."}
• {"endpoint_text":"- Number of (Serious) Adverse Events and Suspected Unexpected Serious Adverse Reaction events during trial course and follow-up.","definition_or_measurement_approach":"Count and classification of AEs, SAEs and SUSARs reported during the trial and follow-up per standard safety reporting procedures."}
• {"endpoint_text":"- OSIBOOST 2-A: Average osimertinib intake reduction over time.","definition_or_measurement_approach":"Average reduction in osimertinib daily intake across participants over time (quantified dosing reduction)."}
• {"endpoint_text":"- Progression-Free Survival (PFS) during osimertinib/cobicistat concomitant treatment.","definition_or_measurement_approach":"Time-to-event measure from start of concomitant treatment to disease progression or death (PFS)."}
• {"endpoint_text":"- CYP3A genotype.","definition_or_measurement_approach":"CYP3A genotyping of blood samples to assess genotype correlations with osimertinib exposure."}
• {"endpoint_text":"- OSIBOOST 2-B: Trough concentrations levels at steady state for osimertinib and AZ5104 in cerebrospinal fluid.","definition_or_measurement_approach":"Measurement of trough concentrations of osimertinib and AZ5104 in cerebrospinal fluid at steady state."}
• {"endpoint_text":"- OSIBOOST 2-B: ctDNA analysis of cerebrospinal fluid.","definition_or_measurement_approach":"Circulating tumour DNA analysis performed on cerebrospinal fluid samples."}

Netherlands

Earliest CTIS Part Ii Submission Date

24-01-2024

Latest Decision Or Authorization Date

10-06-2025

Processing Time Days

503

Number Of Sites

5

Number Of Participants

60

Primary sponsor

Full Name

University Hospital Maastricht

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"ZonMW","duties_or_roles":"Monetary support","organisation_type":""}