OSIMERTINIB for EGFR-mutated non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Written informed consent\n- Negative pregnancy test (blood or urine test)\n- Histological or cytological diagnosis of NSCLC.\n- Clinical stage III/IV disease or a recurrence not amenable for curative treatment intention.\n- Measurable disease according to RECIST 1.1 criteria or equivalent/modified criteria.\n- Any WHO PS.\n- Age 18 years or older.\n- EGFR-mutation in tumor (in cases where tumor tissue is not available for mutation analysis, circulating tumour-DNA (ctDNA) in plasma may serve as inclusion criteria).\n- Treatment-naive with regard to TKI’s.\n- For fertile participants, adequate contraception should be used; intrauterine device, bilateral tubal occlusion, vasectomy or abstinence (a reduced effect of hormonal contraception methods due to the drugs cannot be excluded). Pregnancy should be avoided during treatment and the first 4 months following treatment discontinuation."}

Exclusion criteria

• {"criterion_text":"- Condition incompatible with the study or with the planned treatment.\n- Gastrointestinal conditions incompatible with swallowing or precluding absorption of the study drug.\n- Pregnancy or refusal to use contraceptives.\n- Abnormal findings of blood chemistry not compatible with the study drug according to investigator.\n- History of hypersensitivity to the study drug (or drugs with a similar chemical structure or class) or any excipients.\n- Co-enrolment in other interventional trial if incompatible with ERIS according to investigator (e.g. due to potential drug interactions).\n- Severe hepatic impairment/renal function incompatible with study drug according to investigator.\n- Hereditary conditions with galactose intolerance, total lactase deficiency or glucose -galactose malabsorption.\n- Congenital long QT syndrome.\n- Judgment by the investigator that the subject should not participate in the study, e.g., if the subject is unlikely to comply with study procedures, restrictions and requirements.\n- Present second primary malignancy with metastatic potential.\n- Intake of hypericum perforatum (intake must be interrupted before start of study treatment).\n- All subjects should avoid concomitant use of medications with known interaction with planned treatment, whenever feasible. If the administration of a medication interacts with any of the three investigational treatments and cannot be exchanged or managed in order to avoid interactions the patient is excluded from the trial.\n- Any evidence of severe or uncontrolled systemic diseases which in the investigator’s opinion makes it undesirable for the subject to participate in the trial or which would jeopardise compliance with the protocol. Screening for chronic conditions is not required."}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Time to treatment failure (TTF) of EGFR-inhibitor sequence (total time on TKI)","definition_or_measurement_approach":"Measured as total time on TKI until treatment failure (time to treatment failure)."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Objective response rate (ORR) in first line and the entire sequence of treatment with EGFR-inhibitors","definition_or_measurement_approach":"Objective response rate per tumor response assessments (e.g., RECIST 1.1 as applicable)."}
• {"endpoint_text":"- Disease control rate in (DCR) first line and the entire sequence of treatment with EGFR-inhibitors","definition_or_measurement_approach":""}
• {"endpoint_text":"- Adverse events (AE)","definition_or_measurement_approach":"Collected and reported as adverse events; standard safety reporting per protocol."}
• {"endpoint_text":"- Quality of life (QoL) as assessed through Lung Cancer Symptom Scale (LCSS)","definition_or_measurement_approach":"Measured using the Lung Cancer Symptom Scale (LCSS)."}
• {"endpoint_text":"- Tumor-derived cell-free DNA, i.e. ctDNA, will be analyzed in plasma (and in some cases other fluids, e.g. pleural effusion) to search for potential resistance mechanisms to EGFR-TKIs, to identify early progression and to monitor treatment response. The sensitizing EGFR-mutation, EGFR T790M that confer EGFR-TKI resistance and possibly other tumor mutations, or genetic alterations will be analyzed, either alterations detected in pre-treatment tumor tissue or alterations being screened for in liqui","definition_or_measurement_approach":"ctDNA analysis in plasma (and other fluids where applicable) to detect sensitizing EGFR mutations and resistance mutations (e.g., T790M) for monitoring and identification of resistance mechanisms."}
• {"endpoint_text":"- Proximity Extension Analysis (PEA) protein profiling and RNA expression analysis will be performed on tumor tissue. Obtained markers will subsequently be analyzed with exploratory bioinformatics to set up signaling networks possible to follow longitudinally during the disease course. Furthermore, biomarker candidates may be validated as potential drug candidates.","definition_or_measurement_approach":"PEA protein profiling and RNA expression analysis performed on tumor tissue; exploratory bioinformatics analyses to identify signaling networks and biomarker candidates."}
• {"endpoint_text":"- Bypass signaling is one reason of TKI-resistance. On tumor biopsies prior treatment, bypass signaling mechanisms with focus on Eph signaling components will be analyzed in situ. Upon relapse, the same reactions will be carried out on re-biopsies and differences will be evaluated in the context of response to EGFR-TKI.","definition_or_measurement_approach":"In situ analysis of bypass signaling mechanisms (focus on Eph signaling) on pre-treatment biopsies and re-biopsies at relapse; comparative evaluation versus treatment response."}
• {"endpoint_text":"- Exosomes isolated from plasma and other body fluids will be profiled for mRNA, miRNA and proteins that could be potential key players in resistance mechanisms.","definition_or_measurement_approach":"Profiling of exosomal mRNA, miRNA and proteins from plasma and other fluids to identify potential mediators of resistance."}
• {"endpoint_text":"- Copy number alterations analysis performed on tumor specimen prior treatment and when possible, on tumor re-biopsies at time of progression.","definition_or_measurement_approach":"Copy number alteration analysis on tumor specimens pre-treatment and on re-biopsies at progression."}
• {"endpoint_text":"- Tumor mutational burden (TMB, defined as mutations/megabase) on tumor tissue and potentially on longitudinally assembled blood will be evaluated as a potential marker of resistance and treatment response.","definition_or_measurement_approach":"Assessment of tumor mutational burden (mutations/megabase) on tumor tissue and potentially blood over time as a marker of resistance and response."}

Sweden

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

02-12-2024

Processing Time Days

14

Number Of Sites

10

Number Of Participants

200

Primary sponsor

Full Name

Region Skane

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden