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COMPLETEDPHASE2

Osimertinib (AZD9291) in First-line Locally Advanced or Metastatic NSCLC Patients With EGFR and EGFR T790M

A Phase IIa Clinical Trial to Evaluate the Safety and Efficacy of Osimertinib (AZD9291) in First-line Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC and Concomitant EGFR T790M Mutation at Time of Diagnosis

NCT02841579•MedSIR

View on ClinicalTrials.gov

Summary

The primary goal is to evaluate the efficacy of osimertinib (AZD9291), in terms of the objective response rate in patients with advanced non-squamous NSCLC with EGFR mutations and the EGFR T790M mutation at diagnosis as defined by RECIST 1.1 criteria. Safety and efficacy will also be measured.

Detailed Description

Naïve patients ≥ 18 years of age with histological confirmation of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with an activating EGFR mutation and concomitant T790M mutation. Evidence of measurable or evaluable metastatic disease is required. Primary objective: * To evaluate the efficacy of osimertinib (AZD9291), in terms of the objective response rate in patients with advanced non-squamous NSCLC with EGFR mutations and the EGFR T790M mutation at diagnosis as defined by RECIST 1.1 criteria. Secondary objectives: * To determine the safety and tolerability profile of osimertinib (AZD9291), measured using the number and severity of AEs entered into the Case Report Form (CRF); chemistry, blood count, vital signs, physical examination, weight, ECG and performance status (S). * To determine other efficacy parameters such as progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), duration of response (DOR), disease control rate (DCR), and tumor shrinkage (TS). * To correlate the parameters of clinical response efficacy documented with the EGFR mutational status. * To carry out a longitudinal analysis of EGFR mutations (including the T790M mutation) in plasma and serum. * To determine levels of BIM mRNA as well as mRNA levels of other biomarkers related to EGFR TKI response and determine whether they are predictors of treatment response. * To identify mechanisms of acquired resistance to osimertinib (AZD9291); mutations at the site of covalent binding to the drug (C797) or other mutations in tissue or blood. Type of study: Multicenter, international, single-arm, open-label, non-controlled phase IIa clinical study. Treatment: Patients will be treated with 1 tablet of osimertinib (AZD9291) 80 mg per os (p.o.) daily.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patient aged 18 years or older
•Patients with histological confirmation of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with an activating EGFR mutation and concomitant T790M mutation who are not candidates for local curative treatment.
•Patients with a M1a stage according to the TNM version 7 including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease that is not a candidate for curative treatment (including patients who progress after chemoradiotherapy in stage III disease).
•Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally.
•ECOG (Eastern Cooperative Oncology Group) performance status less than or equal to 2.
•Existence of measurable or evaluable disease (as per RECIST 1.1 criteria). Patients with asymptomatic and stable brain metastases are eligible for the study.
•Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumor or metastatic tumor tissue, within the 60 days prior to study entry.
•Life expectancy ≥12 weeks.
•Adequate hematologic function:
•* Absolute neutrophil count (ANC) \> 1.5 x 109/L
+20 more criteria

Exclusion Criteria

•Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy.
•Patients diagnosed with another lung cancer subtype, patients with mixed NSCLC with predominantly squamous cell cancer, or with any small-cell lung cancer component.
•Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment that have not been confirmed centrally.
•Patients who have received prior antineoplastic treatment for advanced disease.
•Second active neoplasia
•Patients with just one measurable or evaluable tumor lesion that has been resected or irradiated prior to their enrollment in the study.
•Medical history of Interstitial Lung Disease (ILD) induced by drugs, radiation pneumonitis requiring steroid treatment or any evidence of clinically active ILD.
•Corrected QT Interval (QTc) \>470 msec, obtained from 3 ECGs at rest, using the QTc value determined according to the clinical screening ECG machine.
•Any clinically significant abnormality in ECG rhythm, conduction or morphology at rest.
•Any factor that increases the risk of QTc prolongation or risk of irregular heartbeat or sudden inexplicable death under the age of 40 in first-degree relatives or any concomitant medications that prolong the QT interval.

Locations (7)

MedSIR Investigative Site

A Coruña, Spain

MedSIR Investigative Site

Barcelona, Spain

MedSIR Investigative Site

Barcelona, Spain

MedSIR Investigative Site

Bilbao, Spain

MedSIR Investigative Site

Madrid, Spain

MedSIR Investigative Site

Málaga, Spain

MedSIR Investigative Site

Valencia, Spain

Key Dates

Start Date

September 2, 2016

Primary Completion Date

December 1, 2018

Completion Date

February 14, 2020

Last Updated

January 28, 2025

Enrollment

ACTUAL participants

Conditions

Non-Small Cell Lung Cancer

Interventions

Osimertinib

DRUG

A Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)

NCT07190248

Non-small Cell Lung Cancer

View study

RECRUITINGPHASE3

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

NCT06305754

Non-small Cell Lung Cancer (NSCLC)

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 28, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Osimertinib (AZD9291) in First-line Locally Advanced or Metastatic NSCLC Patients With EGFR and EGFR T790M

Inclusion Criteria

Exclusion Criteria

A Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer After Failure of EGFR TKI Therapy (IZABRIGHT-Lung01)

Beamion LUNG-3: A Study to Test Whether Zongertinib Helps People With Surgically Removed, Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment

Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Older Adults w/Adv <50% PD-L1 Non-Small Cell Lung Cancer (NSCLC)