Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)

Adult patients with a histologically or cytologically documented advanced NSCLC not amenable
to curative surgery or radiation with tumors that lack activation EGFR mutations and ALK
fusions are eligible for enrollment. During the initial therapy phase, patients will receive
treatment with Durvalumab along with the Investigator's choice of platinum-based doublet
therapy for squamous NSCLC (nab-paclitaxel plus carboplatin or gemcitabine plus
carboplatin/cisplatin) and non-squamous NSCLC (nab-paclitaxel plus carboplatin or pemetrexed
plus carboplatin/cisplatin) for 4 cycles. Patients who have completed 4 cycles and not
progressed throughout the initial therapy phase will be randomized in a 1:1 ratio into the
maintenance phase of the study to receive either Durvalumab plus placebo or Durvalumab plus
Olaparib maintenance therapy. Patients will receive maintenance treatment until specific
discontinuation criteria are met, including clinical disease progression (as assessed by the
Investigator) or RECIST 1.1-defined radiological Progressive Disease (PD), unacceptable
toxicity, and withdrawal of consent. Tumor evaluation scans will be performed until objective
disease progression as efficacy assessments. All patients will be followed for survival until
the end of the study.

Inclusion Criteria:

- Histologically or cytologically documented Stage IV NSCLC not amenable to curative
surgery or radiation.

Patients must have tumors that lack activating EGFR mutations and ALK fusions.

- (WHO)/(ECOG) performance status of 0 or 1

- No prior chemotherapy or any other systemic therapy for Stage IV NSCLC

- Adequate organ and marrow function without blood transfusions in the past 28 days,

- At least 1 tumor lesion, not previously irradiated, that can be accurately measured as
per RECIST 1.1.

Key Inclusion criteria for randomization to maintenance treatment:

- Documented radiographic evidence of CR, PR, or Stable Disease (SD) as per
Investigator-assessed RECIST 1.1 following 4 cycles of platinum-based chemotherapy.

- Creatinine Clearance (CrCl) ≥51 mL/min calculated by Cockcroft-Gault equation or
measured by 24-hour urine collection.

- Ability to swallow whole oral medications.

Exclusion criteria

- Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology.

- Prior exposure to any chemotherapy agents (except chemotherapy or chemoradiation for
non-metastatic disease), polyadenosine 5'diphosphoribose [poly (ADP ribose)]
polymerase (PARP) therapy, or immunomediated therapy

- Active or prior documented autoimmune or inflammatory disorders.

- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.

- Current or prior use of immunosuppressive medication within 14 days before the first
dose of Investigational Product (IP)

- untreated (CNS) metastases and/or carcinomatous meningitis

- Active infection.

Exclusion criteria to be randomized to maintenance treatment:

• Inability to complete 4 cycles of platinum-based chemotherapy for any reason or
discontinuation of Durvalumab during initial therapy.