Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION)
Condition: Non-small Cell Lung Cancer NSCLC
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Durvalumab; Placebo for Olaparib; Olaparib; Nab-paclitaxel+carboplatin; Gemcitabine+carboplatin; Pemetrexed+carboplatin; Gemcitabine+cisplatin; Pemetrexed+cisplatin
Intervention description: Initial therapy phase: IV infusion q3w for 4 cycles. Maintenance phase: IV infusion q4w.; Matching tablet; 150-mg tablets (2 × 150-mg tablets for 300-mg dose) 100-mg tablet available if dose reductions are required; Standard of Care chemotherapy (squamous and non-squamous patients); Standard of Care chemotherapy (squamous patients only); Standard of Care chemotherapy (non-squamous patients only); Standard of Care chemotherapy (squamous patients only); Standard of Care chemotherapy (non-squamous patients only)
Intervention MeSH terms: Paclitaxel; Cisplatin; Carboplatin; Gemcitabine; Pemetrexed; Durvalumab; Olaparib; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 401.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: NSCLC; Durvalumab; Olaparib; Maintenance; Homologous Recombination Repair (HRR)

Summary:

      This is a randomized, double-blind, multi-center, global Phase II study to determine the
      efficacy and safety of Durvalumab plus Olaparib combination therapy compared with Durvalumab
      monotherapy as maintenance therapy in patients whose disease has not progressed following
      Standard of Care (SoC) platinum-based chemotherapy with Durvalumab as first-line treatment in
      patients with Stage IV non small-cell lung cancer (NSCLC) with tumors that lack activating
      epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK)
      fusions.
    

Eligibility criteria:

        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 the investigator or designee
             using the Cockcroft-Gault equation or measured by 24-hour urine collection.

          -  Ability to swallow whole oral medications.

          -  All patients must provide a formalin-fixed, paraffin embedded tumor sample for
             tissue-based immunohistochemistry staining and DNA sequencing to determine PD-L1
             expression, HRRm status, and other correlatives: either newly acquired or archival
             tumor samples (<3 years old) are acceptable. If available, a newly acquired tumor
             biopsy, collected as part of routine clinical practice, is preferred. If not
             available, an archival sample taken <3 years prior to screening is acceptable. If both
             an archival sample and a fresh tumor biopsy sample are available, both samples should
             be submitted for analysis and must be submitted as different samples using different
             accession numbers. Slides from different blocks cannot be mixed and submitted with the
             same kit.

        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.