Advanced Non-Small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria applicable to all study treatment modules (Groups A/B): • NSCLC with the following features: o Locally advanced or metastatic disease (i.e., advanced NSCLC) not amenable to curative surgery or radiotherapy at study entry. o Histologically or cytologically confirmed adenocarcinoma of the lung harbouring EGFR mutation(s) known to be associated with EGFR TKI sensitivity at diagnosis. o Received only 1 line of therapy, with single-agent osimertinib, for advanced NSCLC, with clinical benefit as judged by investigator discretion. o Evidence 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) ULN and =1.5 x ULN with ALT and AST =1 x ULN Module 2 only: • Possess a mutation at the C797 residue in the EGFR receptor as determined by NGS testing 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 at least one of: EGFR gene amplification, a mutation at the L718 or G724 residue or insertion in exon 20 of the EGFR gene, as determined by NGs testing on tumour tissue collected on or after disease progression on prior monotherapy with osimertinib Module 4 only: • Body weight >30 kg. Module 5 only: • NSCLC with confirmed ALK arrangement as determined by NGS testing on tumour tissue collected on or after disease progression on prior monotherapy with osimertinib. Observational Cohort (Group C): • Patients diagnosed with histopathological transformation to SCLC or SCC (squamous cell carcinoma) following progression on first-line osimertinib • Actionable mutation with potential treatment that is not currently available within ORCHARD Module 6 only: • NSCLC with confirmed RET rearrangement as determined by NGS testing on tumour tissue collected on or after disease progression on prior monotherapy with osimertinib. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: Exclusion Criteria for modules in Groups A/B: •Patients whose disease has progressed within the first 3 months of osimertinib treatment •Must not have experienced a toxicity that led to permanent discontinuation/dose reduction or have any unresolved toxicities from prior osimertinib treatment greater than Common Terminology Criteria for Adverse Event(CTCAE) Grade 1 at the time of starting study treatment •Must not have discontinued osimertinib>60 days prior to first dose of study treatment •Prior or concurrent treatment with systemic anticancer therapy for locally advanced/metastatic NSCLC •Major surgery within 28 days prior to the first dose of study treatment except •Receipt of live attenuated vaccine within 30 days prior to first dose of study treatment •Treatment with warfarin/coumarin analogues within 7 days prior to first dose of study treatment •Diagnosis of small cell lung cancer or squamous cell carcinoma •Spinal cord compression, symptomatic/unstable brain metastases, except for patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for 2 weeks after completion of the definitive therapy and steroids •History of another primary malignancy except for: oMalignancy treated with curative intent and with no active disease for at least 2 years before 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 Hepatitis B/C virus or human immunodeficiency virus(HIV) •Any of the following cardiac criteria: oAny clinically important abnormalities of resting ECG oUnstable atrial fibrillation or 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/stroke or transient ischemic attack in the last 6 months prior to screening oSymptomatic heart failure oSevere valvular heart disease •Inadequate bone marrow reserve or organ function •Creatinine clearance470 msec for women and>450 msec for men at screening. •Acute myocardial infarction currently or within 6 months. •Active gastrointestinal disease or other condition that will interfere with the absorption, distribution, metabolism, or excretion of oral therapy Module 2 only: •Mean resting QTcF >470 msec Module 3 only: •Mean QTcF=450msec Module 4 only: •Active or prior autoimmune or inflammatory disorders(exceptions do apply) •Uncontrolled intercurrent illness and active infection •Any unresolved toxicity National Cancer Institute(NCI) CTCAE Grade=2 from previous anticancer therapy(exceptions do apply) •Osimertinib therapy within 10 days prior to first dose of study treatment •Radiother
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of each treatment by evaluation of objective response rate.;Secondary Objective: To assess the efficacy of each treatment by evaluation of tumour response and overall survival: tumour response (Progression-free survival, Duration of response) and Overall survival. To assess the pharmacokinetics (PK) of each treatment: Plasma/Serum concentrations of specific agents at selected time points. To assess the safety and tolerability of each treatment;Primary end point(s): To assess the efficacy of each treatment by evaluation of objective response rate - Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1) • Objective response rate (ORR);Timepoint(s) of evaluation of this end point: RECIST measurements will be made every 6 weeks (±1 week) for the first 24 weeks relative to the start of study treatment (Cycle 1, Day 1) and every 9 weeks (±1 week) thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond disease progression). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival (OS) Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1): • Progression-free survival (PFS) • Duration of response (DoR) •To assess the pharmacokinetics (PK) of each treatment: plasma/serum concentrations will be measured. •To assess the safety and tolerability of each treatment - • Adverse events/serious adverse events (AEs/SAEs): • Physical examinations • Laboratory findings • Vital signs • Electrocardiogram (ECG). • Left ventricular ejection fraction (LVEF);Timepoint(s) of evaluation of this end point: •OS: Every 12 weeks from progression/safety follow-up visit until cohort final DCO or death. •PFS and DoR: RECIST measurements will be made every 6 weeks (±1week) for the first 24 weeks from the start of study treatment(Cycle 1, Day 1) and every 9 weeks (±1week) thereafter until RECIST 1.1 defined disease progression or cessation of study treatment(if treating beyond disease progression) •PK: measurement of plasma/serum concentrations for specific drugs at selected time points. •Safety and tolerability: Collection of AE/SAEs from the time of signature of the pre-screening ICF throughout the treatment period, including the safety follow-up. All other assessments performed throughout the treatment period(including the safety follow up). | — |
Countries
Denmark, Italy, Japan, Korea, Republic of, Netherlands, Norway, Spain, Sweden, United States
Contacts
Public ContactInformation Centre
AstraZeneca
Outcome results
None listed