OSIMERTINIB for Non-small cell lung cancer (EGFR mutation-positive)

Inclusion criteria

• {"criterion_text":"- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n- WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.\n- Life expectancy >12 weeks at Day 1.\n- At least 1 lesion, not previously irradiated that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis of ≥15 mm) with CT or MRI, and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumor assessment scans.\n- Female patients who are not abstinent (in line with the preferred and usual lifestyle choice of the patient) and intend to be sexually active with a male partner must be using highly effective contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of IP or must have evidence of nonchild-bearing potential by fulfilling 1 of the following criteria at screening: a. Post-menopausal, defined as more than 50 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments b. Women under 50 years old would be considered as postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution c. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.\n- Male patients must be willing to use barrier contraception.\n- Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses.\n- For patients who agree to the optional genetic testing, provision of signed and dated genetic testing section of the written Main ICF prior to collection of a sample for genetic analysis for inclusion in the optional genetic research as allowed by local regulations.\n- Male or female, at least 18 years of age; patients from Japan at least 20 years of age.\n- Pathologically confirmed nonsquamous NSCLC. NSCLC of mixed histology is allowed.\n- Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC (per Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology), not amenable to curative surgery or radiotherapy.\n- The tumor harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing.\n- Mandatory provision of a baseline plasma sample and an unstained, archival tumor tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.\n- Patients must have untreated advanced NSCLC not amenable to curative surgery or radiotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior to the development of recurrent disease."}

Exclusion criteria

• {"criterion_text":"- Spinal cord compression and unstable brain metastases. Patients with stable brain metastases who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids can be enrolled. Patients with asymptomatic brain metastases can be eligible for inclusion if in the opinion of the Investigator immediate definitive treatment is not indicated.\n- Prior treatment with an EGFR-TKI\n- Major surgery within 4 wks of the 1st dose of IP. Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery are permitted\n- Radiotherapy treatment to more than 30% of the bone marrow/with a wide field of radiation within 4 wks of the 1st dose of IP\n- Current use of (or unable to stop use prior to receiving the 1st dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3 wks prior)\n- Participation in another clinical study with an investigational product during the 4 wks prior to Day 1. Patients in the follow-up period of an interventional study are permitted\n- Involvement in the planning &/or conduct of the study (applies to both AZ staff & staff at the study site)\n- Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions & requirements\n- Previous treatment allocation (safety run in)/randomization (randomization period) in the present study\n- Currently pregnant (confirmed with positive preg. test)/breastfeeding\n- History of hypersensitivity to active or inactive excipients of IP or drugs with a similar chemical structure/class to IP\n- Past medical history of ILD, drug induced ILD, radiation pneumonitis that required steroid treatment/any evidence of clinically active ILD\n- In addition, the following are considered criteria for exclusion from the exploratory genetic research: Prior allogeneic bone marrow transplant, Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection\n- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. Active infection will include any patients receiving treatment for infection.\n- Any of the ff: cardiac criteria a.Mean resting corrected QT interval >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value b.Any clinically important abnormalities in rhythm, conduction/morphology of resting ECG; eg, complete left bundle branch block, 3rd degree heart block, 2nd degree heart block c.Any factors that increase the risk of QTc prolongation/risk of arrhythmic events such as electrolyte abnormalities including serum/plasma potassium, magnesium & calcium below the LLN, heart failure, congenital long QT syndrome, family history of long QT syndrome/unexplained sudden death under 40 years of age in first degree relatives/any concomitant medication known to prolong the QT interval & cause Torsades de Pointes\n- Inadequate bone marrow reserve/organ function as demonstrated by any of the ff: lab values a.Absolute neutrophil count below the lower limit of normal b.Platelet count below the LLN c.Hemoglobin <90 g/L d.ALT >2.5 x the upper limit of normal if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases e.AST >2.5 x ULN if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases f.Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia)/liver metastases g.Creatinine clearance <60 mL/min calculated by Cockcroft & Gault equation/24hr urine collection\n- Any concurrent &/other active malignancy that has required treatment within 2 years of 1st dose of IP\n- Any unresolved toxicities from prior systemic therapy (eg, adjuvant chemo) greater than CTCAE Grade 1 at the time of starting study treatment except for alopecia & Grade 2 prior platinum-therapy related neuropathy\n- Refractory nausea & vomiting, chronic GI diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib\n- Prior treatment with any systemic anti-cancer therapy for advanced NSCLC not amenable to curative surgery or radiation including chemo, biologic therapy, immunotherapy, or any investigational drug. Prior adjuvant & neo-adjuvant therapies (chemo, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with/without regimens including immunotherapy, biologic therapies, investigational agents are permitted if treatment was completed at least 12 months prior to the development of recurrent disease"}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS) using Investigator assessment as defined by RECIST 1.1.","definition_or_measurement_approach":"Investigator assessment as defined by RECIST 1.1."}

Secondary endpoints

• {"endpoint_text":"- OS; Landmark OS at 1, 2, and 3 years; ORR, DoR; depth of response; DCR by Investigator","definition_or_measurement_approach":"Overall survival (OS), landmark OS at specified years; objective response rate (ORR), duration of response (DoR), depth of response, disease control rate (DCR) assessed by Investigator."}
• {"endpoint_text":"- PFS2; TFST; TSST","definition_or_measurement_approach":"PFS2, TFST and TSST (abbreviations listed; specific definitions not provided in source)."}
• {"endpoint_text":"- Change from baseline and time to deterioration in EORTC QLQ-C30; Change from baseline and time to deterioration in EORTC QLQ-LC13","definition_or_measurement_approach":"Patient-reported outcomes measured using EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires; analyses of change from baseline and time to deterioration."}
• {"endpoint_text":"- Steady-state plasma concentrations and appropriate PK parameters (CLss/F, Cmax,ss Cmin,ss and AUCss) of osimertinib and its metabolite, AZ5104 will be summarized.","definition_or_measurement_approach":"Pharmacokinetic sampling to summarize steady-state plasma concentrations and PK parameters (CLss/F, Cmax,ss, Cmin,ss, AUCss) for osimertinib and AZ5104."}
• {"endpoint_text":"- Concordance of EGFR mutation status between the local EGFR mutation test and the central cobas® EGFR Mutation Test v2 results from tumor samples with evaluable results.","definition_or_measurement_approach":"Comparison of local EGFR mutation test results with central cobas® EGFR Mutation Test v2 on tumor samples to assess concordance."}
• {"endpoint_text":"- PFS by Investigator by plasma EGFR mutation status.","definition_or_measurement_approach":"Investigator-assessed PFS analyzed by plasma EGFR mutation status."}

Czechia

Earliest CTIS Part Ii Submission Date

11-06-2024

Latest Decision Or Authorization Date

09-01-2025

Processing Time Days

212

Number Of Sites

4

Number Of Participants

21

France

Earliest CTIS Part Ii Submission Date

11-06-2024

Latest Decision Or Authorization Date

08-01-2025

Processing Time Days

211

Number Of Sites

4

Number Of Participants

6

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden