Study in patients with Non-Small Cell Lung Cancer whose disease has got worse on Osimertinib treatment.

Phase 1

• Conditions: Advanced Non-Small Cell Lung Cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003974-29-ES
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-11
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 150

Inclusion Criteria

Inclusion criteria applicable to all study treatment modules (Groups A/B):
•NSCLC with the following features –
oLocally advanced or metastatic disease (i.e., advanced NSCLC) not amenable to curative surgery or radiotherapy at study entry.
oHistologically or cytologically confirmed adenocarcinoma of the lung harbouring EGFR mutation(s) known to be associated with EGFR TKI sensitivity at diagnosis.
oReceived only 1 line of therapy, with single-agent osimertinib, for advanced NSCLC, with clinical benefit as judged by investigator discretion.
oEvidence of radiological disease progression on first-line monotherapy with osimertinib 80mg once daily.
•Suitable for a mandatory biopsy defined as having an accessible tumour and a stable clinical condition that will allow the patient to tolerate the procedure. The biopsy should be performed within 60 days prior to the planned first dose of study treatment.
•Patients must have measurable disease per RECIST 1.1.
•World Health Organisation (WHO) performance status 0 or 1 with no deterioration between screening and the first dose of study treatment and a minimum life expectancy of 12 weeks.
•Adequate coagulation parameters, defined as: International Normalisation Ratio (INR) <1.5 × ULN and activated partial thromboplastin time <1.5 × ULN unless patients are receiving therapeutic anti-coagulation which affects these parameters.
•Patients with known tumour thrombus or deep vein thrombosis are eligible if clinically stable on low molecular weight heparin, factor Xa inhibitors or thrombin inhibitors for =2 weeks.
•Willingness to adhere to the study treatment-specific contraception requirements.
Module 1:
•NSCLC with confirmed MET amplification as determined by Next Generation Sequencing on tumour tissue collected on or after disease progression on prior monotherapy with osimertinib.
•No transfusion of blood or blood-derived products in the past 2 weeks
Module 2:
•Possess a mutation at the C797 residue in the EGFR receptor as determined by Next Generation Sequencing on tumour tissue collected on or after disease progression on prior monotherapy with osimertinib
Module 3:
•For the Group A (biomarker matched) cohort only, must possess EGFR amplification as determined by Next Generation Sequencing on tumour tissue collected on or after disease progression on prior monotherapy with osimertinib
Module 4:
•No prior exposure to immune-mediated therapy including, but not limited to, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccine.
•Body weight >30 kg.
Observational Cohort (Group C):
•Patients diagnosed with histopathological transformation to SCLC or SCC (squamous cell carcinoma) on the mandatory baseline biopsy
•Actionable mutation with potential treatment that is not currently available within ORCHARD
•Screen failures for study treatment module.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes

Exclusion Criteria

Exclusion Criteria applicable to all study treatment modules (Groups A/B):
•Patients whose disease has progressed within the first 3 months of osimertinib treatment
•Patients must not have experienced a toxicity(-ies) that led to permanent discontinuation or dose reduction of prior osimertinib or have any unresolved toxicities from prior osimertinib treatment greater than CTCAE Grade 1 at the time of starting study treatment
•Patients should not have discontinued osimertinib >60 days prior to the first dose of study treatment
•Prior or concurrent treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug (exceptions do apply)
•Major surgery within the 28 days prior to the first dose of study treatment except:
oAfter minor surgery, at least 7 postoperative days must elapse before study treatment is initiated. After placement of vascular access, this waiting period is not required.
•Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment.
•Treatment with warfarin/coumarin analogues within 7 days prior to the first dose of study treatment
•Diagnosis of small cell lung cancer (SCLC) or squamous cell carcinoma (SCC)
•Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids.
•Allogenic organ transplantation
•History of another primary malignancy except for:
oMalignancy treated with curative intent and with no known active disease for at least 2 years before the first dose of study treatment.
oAdequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease
oAdequately treated carcinoma in situ without evidence of disease.
oLocalised non-invasive primary disease under surveillance.
•Active infection, including infections with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
•Pregnancy or breastfeeding in female patients
•Any of the following cardiac criteria:
oAny clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
oUnstable atrial fibrillation or unstable cardiac arrhythmia with a ventricular rate >100 bpm on an ECG at rest.
oUncontrolled hypertension
oUncontrolled angina or acute coronary syndrome within 6 months prior to screening.
oAt risk for brain perfusion problems or stroke, or transient ischemic attack in the last 6 months prior to screening
oSymptomatic heart failure - prior or current cardiomyopathy.
oSevere valvular heart disease
•Inadequate bone marrow reserve or organ function
•Creatinine clearance <50 mL/min, calculated by Cockcroft-Gault equation

Module 1,2 & 3 only:
•Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid tr

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified