- Patients must have completed all standard of care therapy that the treating
oncologist thinks is appropriate. As a minimum patients must have failed one or more
lines of treatment (either radiological documentation of disease progression or due
- Patients who have progressed after surgical resection and adjuvant therapy will be
eligible for entry without the need for the administration of first line metastatic
therapy, if they have progressed within 6 months of completing their adjuvant
- Patients will also be eligible without the necessity for first line regimen if they
have relapsed within 6 months of completion of definitive chemoradiation.
- Consented and provided an adequate specimen to adequately characterise the molecular
genotype of the tumour in the molecular pre-screening according to the molecular
exclusion rules (see section 6.4 for definition of an adequate sample).
- Histological or cytologically confirmed NSCLC stage III (not suitable for radical
radiotherapy or surgery) or stage IV. This includes patients who may have abnormal
histology, but IHC strongly support either squamous cell carcinoma (p63 positivity)
or adenocarcinoma (Thyroid transcription factor 1 [TTF1] positivity). If a physician
and pathologist are convinced after multi-disciplinary review that the patient has
stage III or IV NSCLC but where all the IHC is negative and the morphology does not
distinguish a specific sub-type, these patients will be eligible for non-histology
- CT scan of head, chest and abdomen within 28 days of treatment demonstrating
measurable disease as per RECIST version 1.1.
- Adequate haematological function within 7 days of treatment.
- Haemoglobin 90 g/L.
- Absolute neutrophil count (ANC) 1.5 x 109/L.
- Platelets 100 x 109/L.
- Adequate hepatic function within 7 days of treatment in patients with no liver
metastasis (see arm specific entry criteria for adequate hepatic function in patients
with liver metastases).
- Total serum bilirubin 1.5 x upper limit of normal (ULN).
- Alanine transferase (ALT) 2.5 x ULN.
- Aspartate transferase (AST) 2.5 x ULN.
- Adequate renal function within 7 days of treatment.
- Creatinine clearance (CLcr) >50 ml/min (measured or calculated by Cockcroft and
- Age 18 years.
- Females must agree to use adequate contraceptive measures, should not be breast
feeding and must have a negative pregnancy test prior to start of dosing if of
child-bearing potential or must have evidence of non-child-bearing potential by
fulfilling one of the following criteria at screening:
- Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least
12 months following cessation of all exogenous hormonal treatments
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral
oophorectomy or bilateral salpingectomy but not tubal ligation.
- Women aged under 50 years old would be consider postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of exogenous hormonal
treatments and with luteinizing hormone (LH) and follicle stimulating hormone
(FSH) levels in the post-menopausal range for the institution.
- Provision of signed and dated, written informed consent prior to any study specific
procedures, sampling and analyses.
- Major surgery (excluding placement of vascular access), chemotherapy, radiotherapy,
any investigational agents or other anti-cancer therapy within 4 weeks prior to
- Nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease)
that would preclude adequate absorption.
- Any psychological, familial, sociological or geographical condition hampering
- Concurrent malignancies or invasive cancers diagnosed within past 3 years except for
adequately treated basal cell carcinoma of the skin and in situ carcinoma of the
- Judgement by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
- Any unresolved toxicity of grade 2, 3 or 4 from previous treatment (excluding
alopecia) at Registration (see CTCAE).
- Patients who have previous symptomatic brain metastases or spinal cord compression
are excluded unless they have had adequate treatment, no evidence of progression or
symptoms, and have had no requirement for steroid treatment in the previous 28 days
before commencement of trial treatment.
- Patients with asymptomatic brain metastases picked up at screening CT scan are not
excluded providing that in the view of the investigator they do not require immediate
radiotherapy or surgical intervention, and have had no requirement for steroid
treatment in the previous 28 days before commencement of trial treatment.
- As judged by the investigator, any evidence of severe or uncontrolled systemic
diseases, including active bleeding diatheses, or active infection including
hepatitis B, hepatitis C and human immunodeficiency virus. Screening for chronic
conditions is not required.
- Pregnant or breast-feeding women
Cardiac exclusion criteria and performance status eligibility criteria are detailed within
The National Lung Matrix Trial arm-specific eligibility criteria.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both