Parp Inhibitor in Advanced Non-Small Cell Lung Cancer (PIN)

Inclusion Criteria - Registration (Stage 1): * Histological diagnosis of NSCLC. Histology can be either squamous or non-squamous. * Stage IIIB or stage IV lung cancer that is not amenable to curative therapy. * Have had no prior systemic chemotherapy for advanced NSCLC. Previous adjuvant or neoadjuvant chemotherapy for non-advanced disease is acceptable. Prior treatment with an oral targeted therapy for e.g. EGFR/ALK or other driver- oncogene mutated lung cancer is allowed. Immunotherapy e.g. with a PD1 or PDL1 targeted agent is allowed. * Patients who have already started their induction chemotherapy are not eligible for stage 1 of the trial * Eligible to receive standard platinum doublet-based chemotherapy. * Men or women, aged 18 or over and capable of giving informed consent. * Willing to consent to provide tissue and blood for translational research. * Informed consent prior to any study specific procedures. Exclusion Criteria - Registration (Stage 1): * Evidence of small cell, large cell neuroendocrine or carcinoid histology. * Have a serious or uncontrolled medical condition that could compromise the patients' ability to adhere to the protocol. * Have a secondary malignancy (except adequately treated non-melanomatous skin cancer, or other cancer considered cured by surgical resection or radiation). Patients who have had another malignancy in the past but have been disease free for more than 5 years are eligible. * Previous treatment with PARP inhibitors * Uncontrolled gastrointestinal disorders such as active diverticulitis or colitis, or any major GI resection which could have an impact on patients' ability to absorb Olaparib. * Myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML). Inclusion Criteria - Randomisation (Stage 2): * Confirmed diagnosis of NSCLC (either squamous or non-squamous). Stage IIIB or stage IV that is not amenable to curative therapy. * ECOG performance status 0-1 * Evidence of radiological response to induction chemotherapy, from the pre-treatment to baseline. This can include mixed stable/response or evidence of tumour shrinkage that does not reach the criteria of partial response according to RECIST. * Have had no prior systemic chemotherapy for advanced NSCLC. Previous adjuvant or neoadjuvant chemotherapy for non-advanced disease is acceptable. Previous palliative radiotherapy to non-target metastases is allowed provided no more than 25% of the bone marrow volume is irradiated. Irradiated sites cannot include the sites of measurable disease unless clear tumour progression has been documented in them since the end of radiation therapy. Patients who have had adjuvant therapy and then progressed after a year of completing adjuvant therapy are eligible. Patients who have received an oral inhibitor for molecularly stratified subgroups e.g. EGFR or ALK mutated lung cancer, are allowed. Immunotherapy e.g. with a PD1 or PDL1 targeted agent is allowed. * Adequate organ function, including the following: 1. Adequate bone marrow reserve: White cell count ≥ 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, haemoglobin ≥ 90g/L. 2. Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) ≤ 2.5 x ULN. ALP, AST, and ALT ≤ 5 x ULN is acceptable if the liver has tumour involvement. 3. Renal: calculated creatinine clearance (CrCl) ≥ 50mL/min using Cockcroft-Gault or Wright formula, serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN). 4. If blood count/morphology suggestive of MDS/AML, no features suggestive of MDS/AML on peripheral blood smear. * Patients with reproductive potential (male or female), who are sexually active for the duration of the trial or the drug washout period, should be prepared to use two effective forms of contraception. * Men or women, aged 18 or over. * Willing to consent to provide tissue and blood for translational research. * Patients must provide informed consent prior to any study specific procedures. * There should be no more than 42 days between day 1 of the last cycle of induction chemotherapy and starting Olaparib/placebo. Exclusion Criteria - Randomisation (Stage 2): * Evidence of small cell, large cell neuroendocrine or carcinoid histology. * Patients with radiological disease progression or stable disease after induction chemotherapy * Have received treatment with an agent that has not received regulatory approval, within 30 days of study entry. * Have had a blood transfusion within 28 days prior to commencing Olaparib or have a WBC \<3 x 109/L * Have received yellow fever vaccination in the 30 days prior to randomisation. * Difficulty swallowing. * Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases e.g. involving complete surgical removal or radical radiotherapy to a solitary CNS metastasis). A * Concurrent administration of any other systemic antitumour therapy. * Have a serious or uncontrolled medical condition that would compromise the patient's ability to adhere to the protocol. * Diagnosis of a second malignancy (except adequately treated non-melanomatous skin cancer, or other cancer that is considered cured by surgical resection or radiation). Patient who had another malignancy in the past but have been disease free for more than 5 years are eligible. * Previous treatment with PARP inhibitors. * Uncontrolled gastrointestinal disorders such as active diverticulitis or colitis, or any major GI resection which could have an impact on patients' ability to absorb Olaparib. * Myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML). * Pregnant or breastfeeding.