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Osimertinib

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An oral, potent, selective, irreversible inhibitor of both EGFR-tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer

Osimertinib is an oral, potent, selective, irreversible inhibitor of both EGFR-tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer with a significant selectivity margin over wild type EGFR.

Zosia Piotrowska, MD

A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib.

Study design This is a phase II, open-label, single-arm tissue and plasma acquisition study assessing the efficacy, safety and underlying resistance mechanisms of osimertinib (80 mg orally, once daily) as first-line treatment in patients with locally advanced or metastatic EGFR mutation positive non-small cell lung cancer who are EGFR tyrosine kinase inhibitor treatment-naïve and eligible for first-line treatment. Participants with EGFR mutation-positive non-small cell lung cancer will be required to consent to 2 mandatory tumour biopsies to be considered for enrolment in this study. The first biopsy will be done prior to initiating treatment with osimertinib and the second biopsy will be obtained any time between Investigator assessed, Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)-defined progression and before the start of any new anticancer treatment. A third optional biopsy may be taken during the course of treatment at the Investigator's discretion if the patient consents and if clinically feasible. Tumour tissue and plasma samples will be collected and examined for genetic and non genetic aberrations that may be important in determining response and resistance to the treatment that participants will receive as a part of their cancer care. Patients should continue on osimertinib until progression or until other treatment discontinuation criteria are met. However, if patients continue to show clinical benefit to treatment as judged by the Investigator, patients may continue to receive osimertinib beyond RECIST 1.1-defined progression. Therefore, there is no maximum duration of treatment. Tumour assessments will be performed at baseline and then every 8 weeks from study enrolment until 3.5 years, and then every 10 weeks until RECIST 1.1-defined. Patients will be followed up for a period of 28 days following discontinuation of osimertinib. Target patient population Male and female patients aged 18 years and over with locally advanced or metastatic pathologically confirmed adenocarcinoma of the lung, not amenable to curative surgery or radiotherapy. Patients will have a tumour that harbours one of the EGFR mutations known to be associated with EGFR tyrosine kinase inhibitor sensitivity, either alone or in combination with other EGFR mutations (EGFR mutation status determined by a local laboratory). Patients must be EGFR tyrosine kinase inhibitor treatment-naïve and eligible to receive first line treatment with osimertinib. Osimertinib is an oral, potent, selective, irreversible inhibitor of both EGFR tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer with a significant selectivity margin over wild type EGFR. Osimertinib (80 mg orally, once daily) will be administered. Doses may be reduced to 40 mg if needed.

A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib

A Multicentre, Open-label, Single-arm, Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

To summarize the safety and tolerability profile of osimertinib as first-line EGFR tyrosine kinase inhibitor therapy for patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer

To characterize the frequency of genetic and proteomic markers at disease progression regardless of their prevalence.

PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed RECIST 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression.

ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later.

DoR is defined as the time from the date of first documented response, (that is subsequently confirmed) until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint.

TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.

TFST is defined as the time from the date of first dose of osimertinib to the earlier of the date of anticancer therapy start date following study treatment discontinuation, or death.

Percentage of patients who have a best overall response, complete response, partial response or stable disease.

PFS will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Epidermal growth factor receptor (EGFR) Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived circulating tumour deoxyribonucleic acid (ctDNA).

ORR will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.

TTD will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.

Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions. Tumour shrinkage/depth of response will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.

The patient characteristics will include: gender (male/female), age (\<65yrs/\>65yrs), race (Asian/non Asian), and WHO Performance Status (0/1). These will be summarized by subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib	NCT03239340	EGFR Mutation P...	Osimertinib	18 Years - 130 Years	AstraZeneca
A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib	NCT03239340	EGFR Mutation P...	Osimertinib	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for egfr, nsclc, lung cancer, biopsy, molecular profiling