Osimertinib for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Provision of informed consent prior to any study specific procedures.\n- Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICFs and in this protocol\n- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative\n- Male or female, aged at least 18 years.\n- Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.\n- MRI or contrast CT scan of the brain must be done prior to surgery as it is considered standard of care. Participants in whom this was not done within 42 days (6 weeks) prior to surgery may still be enrolled if appropriate imaging is performed prior to enrolment, ie, MRI or CT of the brain.\n- Participants must be classified post-operatively as Stage II, IIIA, or IIIB on the basis of surgical pathologic criteria. Staging will be according to the pTNM (pathologic tumour, node, metastasis) staging system for lung cancer (AJCC 8th Edition Staging Manual\n- Confirmation by the local laboratory that the tumour harbours one of the following EGFR mutations: -1 of the 2 common EGFR mutations (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo T790M and excluding all exon 20 insertions (Common EGFRm Cohort); or - Uncommon EGFR mutations G719X, S768I, and L861Q, either alone, in combination with each other, or in combination with other uncommon EGFR mutations (excluding all exon 20 insertions) (Uncommon EGFRm Cohort)\n- Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour. Resection may be accomplished by open or Video Associated Thoracic Surgery techniques"}

Exclusion criteria

• {"criterion_text":"- Major surgery (including primary tumour surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study drug\n- Participants currently receiving (or unable to stop use prior to receiving the first dose of study intervention) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior to first dose) (Appendix G). All participants must try to avoid concomitant use of any medications, herbal supplements, and/or ingestion of food with known inducer effects on CYP3A4. Participants with any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy will not be eligible.\n- Participants who have had only segmentectomies or wedge resections\n- History of other malignancies, except: adequately treated non- melanoma skin cancer, curatively treated in situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years before the start of study intervention and that, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy\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 participant to participate in the study or that would jeopardise compliance with the protocol; or active infection (eg, participants receiving treatment for infection including, hepatitis C and human immunodeficiency virus, or active, uncontrolled HBV infection). - Screening for chronic conditions is not required. -\tActive infection will include any participants receiving treatment for infection. Should participants with HBV infection be included, they are only eligible if they meet all the following criteria: -Demonstrated absence of HCV co-infection or history of HCV co-infection -Demonstrated absence of HIV infection -Participants with active HBV infection are eligible if they are: Receiving anti-viral treatment for at least 6 weeks prior to study intervention, HBV DNA is suppressed to < 100 IU/mL and transaminase levels are below ULN. -\tParticipants with a resolved or chronic HBV infection are eligible if they are: Negative for HBsAg and positive for hepatitis B core antibody (anti-HBc IgG or total anti-HBc Ab). In addition, participants must be receiving anti-viral prophylaxis for 2 to 4 weeks prior to study intervention. Positive for HBsAg, but for > 6 months have had transaminases levels below ULN and HBV DNA levels below < 100 IU/mL (ie, are in an inactive carrier state). In addition, participants must be receiving anti-viral prophylaxis for 2 to 4 weeks prior to study intervention. Refer to Section 5.3. Should participants with HIV infection be included, they are only eligible if they meet all the following criteria: − Demonstrated absence of HBV/HCV co-infection − Undetectable viral RNA load for 6 months − CD4+ count of > 350 cells/μL − No history of acquired immunodeficiency syndrome-defining opportunistic infection within the past 12 months − Stable for at least 4 weeks on the same anti-HIV medications\n- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib\n- Any of the following cardiac criteria: -\tMean resting QTc interval > 470 msec, obtained from 3 ECGs. -\tAny clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, eg, complete left bundle branch block, third-degree heart block, second-degree heart block. -\tParticipant with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including: o\tSerum/plasma potassium < LLN o Serum/plasma magnesium < LLN o\tSerum/plasma calcium < LLN -\tHeart failure, congenital long QT interval (QT) syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause TdP.\n- Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD\n- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: -\tAbsolute neutrophil count < 1.5 × 109 /L. -\tPlatelet count < 100 × 109 /L. -\tHaemoglobin < 90 g/L. - ALT > 2.5 × the ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases. -\tAST > 2.5 × ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases. -\tTotal bilirubin > 1.5 × ULN if no liver metastases or > 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases. - Creatinine > 1.5 × ULN concurrent with CrCl < 50 mL/min (measured or calculated by Cockcroft and Gault equation, Appendix K); confirmation of CrCl is only required when creatinine is > 1.5 × ULN"}

Primary endpoints

• {"endpoint_text":"- DFS at 5 years per the investigator's assessment in the Common EGFRm Cohort","definition_or_measurement_approach":"Investigator's assessment of disease-free survival (DFS) at 5 years in the Common EGFRm Cohort (per protocol/investigator assessment)"}

Secondary endpoints

• {"endpoint_text":"- The measure of interest is the proportion of participants alive and disease-free at 3, 4, and 5 years","definition_or_measurement_approach":"Proportion of participants alive and disease-free at 3, 4, and 5 years"}
• {"endpoint_text":"- The measure of interest is the proportion of participants alive and disease-free at 3 and 4 years","definition_or_measurement_approach":"Proportion of participants alive and disease-free at 3 and 4 years"}
• {"endpoint_text":"- The measure of interest is the proportion of participants alive at 3, 4, and 5 years","definition_or_measurement_approach":"Proportion of participants alive at 3, 4, and 5 years"}

Spain

Earliest CTIS Part Ii Submission Date

08-12-2023

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

340

Number Of Sites

8

Number Of Participants

105

Italy

Earliest CTIS Part Ii Submission Date

08-12-2023

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

628

Number Of Sites

13

Number Of Participants

20

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Parexel International Corp.

Responsibilities

Sponsor duties codes: 1,10,12,13,2,5,6,7,8,9; contact email: Clinicaltrial.Enquiries@parexel.com

Third parties

• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Sponsor duties codes: 1,10,12,13,2,5,6,7,8,9 (as listed in Part II thirdParties.sponsorDuties)","organisation_type":"Pharmaceutical company"}