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

NCT02841579 | Completed Phase 2 Results

• 2 other identifiers: MedOPP1122015-004828-66
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Defined as the percentage of patients who achieved complete response \[CR\] and partial response \[PR\] to treatment in accordance to the revised RECIST guidelines (version 1.1) for target lesions: CR, disappearance of all target lesions; PR: at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Through study completion. From baseline up to approximately 28 months.

Secondary Outcomes (13)

• Overall Survival (OS)

  Through study completion. From baseline up to 41 months.

• Duration of Response (DoR)

  Through study completion. From baseline up to 41 months.

• Disease Control Rate

  Through study completion. From baseline up to 41 months.

• Tumor Shrinkage

  Through study completion. From baseline up to 41 months.

• Overall Plasma EGFR Mutation Status at Baseline

  Baseline

Study Arms (1)

Osimertinib

EXPERIMENTAL

The patients will be treated with 1 tablet of osimertinib (AZD9291) 80 mg per os (p.o.) daily. Patients will receive study treatment until disease progression or occurrence of unacceptable side effects up to 78 weeks from the time of the first administered dose.

Drug: Osimertinib

Interventions

Osimertinib DRUG

The patients will be treated with 1 tablet of osimertinib (AZD9291) 80 mg per os (p.o.) daily up to 78 weeks from the time of the first administered dose.

Also known as: AZD9291

Osimertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• platelet count \> 100.0 x109/L
• hemoglobin \> 9.0 g/dL (\> 6.2 mmol/L).
• Adequate coagulation: INR ≤ 1.5.
• Adequate liver function
• Adequate renal function.

You may not qualify if:

• 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.
• Uncontrolled, active or symptomatic metastases of CNS, carcinomatous meningitis or leptomeningeal disease indicated by known clinical symptoms, cerebral edema and/or progressive neoplasia. Patients with history of CNS metastasis or compression of the spinal cord are eligible if they have received local final treatment (e.g., radiotherapy, stereotactic surgery) and if they have remained clinically stable without using anticonvulsants and corticosteroids for a minimum of 4 weeks prior to the first day of study treatment.
• Refractory nauseas and vomiting, chronic gastrointestinal disease, inability to swallow study drug or significant intestinal resection that restricts the adequate absorption of osimertinib (AZD9291).
• Patients who have had a surgical procedure unrelated to the study within 7 days prior to the administration of the drug or a significant traumatic lesion during the 4 weeks prior to starting the administration of the study drug, patients who have not recovered from the side effects of any major surgery or patients who might need major surgery during the course of the study.
• Pregnant or breastfeeding women. Women of childbearing potential, including women who had their last menstrual period within the last two years, must have a negative serum or urine pregnancy test in the 7 days prior to the start of the treatment.
• Patients who are not willing to use an adequate contraception method until 12 months after the last dose of study treatment.

Sponsors & Collaborators

• MedSIR: lead
• AstraZeneca: collaborator

Study Sites (7)

MedSIR Investigative Site

A Coruña, 15706, Spain

Location

MedSIR Investigative Site

Barcelona, 08026, Spain

Location

MedSIR Investigative Site

Barcelona, 08028, Spain

Location

MedSIR Investigative Site

Bilbao, 48903, Spain

Location

MedSIR Investigative Site

Madrid, 28006, Spain

Location

MedSIR Investigative Site

Málaga, 29010, Spain

Location

MedSIR Investigative Site

Valencia, 46015, Spain

Location

Related Publications (1)

• Majem M, Sullivan I, Viteri S, Lopez-Vivanco G, Cobo M, Sanchez JM, Garcia-Gonzalez J, Garde J, Sampayo M, Martrat G, Malfettone A, Karachaliou N, Molina-Vila MA, Rosell R. First-line osimertinib in patients with epidermal growth factor receptor-mutant non-small-cell lung cancer and with a coexisting low allelic fraction of Thr790Met. Eur J Cancer. 2021 Dec;159:174-181. doi: 10.1016/j.ejca.2021.09.039. Epub 2021 Nov 8.

  PMID: 34763195 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Rafael Rosell
• Organization: Catalan Institute of Oncology, Institut d'Investigació en Ciències, de la Salut Germans Trias i Pujol

rrosell@iconcologia.net

+34 935 543 050

Study Officials

• Rafael Rosell, MD, PhD

  Catalan Institute of Oncology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: July 22, 2016
• Study Start: September 2, 2016
• Primary Completion: December 1, 2018
• Study Completion: February 14, 2020
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7)