Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON).
Condition: Non Small Cell Lung Cancer NSCLC
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Durvalumab; Tremelimumab; Abraxane + carboplatin; Gemcitabine + cisplatin; Gemcitabine + carboplatin; Pemetrexed + carboplatin; Pemetrexed + cisplatin
Intervention description: IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until disease progression or other discontinuation criteria; IV infusions every 3 weeks for 12 weeks (4 cycles). An additional dose of tremelimumab will be administered in the week 16.; Standard of care chemotherapy (squamous and non-squamous patients): Abraxane 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Carboplatin Area under the plasma drug concentration-time curve (AUC) 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.; Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.
Intervention MeSH terms: Cisplatin; Carboplatin; Gemcitabine; Pemetrexed; Durvalumab; Albumin-Bound Paclitaxel; Tremelimumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1186.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: NSCLC; Programmed cell death ligand 1 (PD-L1); Durvalumab; Tremelimumab; Progression-free survival (PFS); Overall survival (OS)

Summary:

      This is a randomized, open-label, multi-center, global, Phase III study to determine the
      efficacy and safety of durvalumab + tremelimumab combination therapy + Standard of care (SoC)
      chemotherapy or durvalumab monotherapy + SoC chemotherapy versus SoC chemotherapy alone as
      first line treatment in patients with metastatic 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:

        For inclusion in the study, patients should fulfill the following criteria:

          1. Aged at least 18 years.

          2. Histologically or cytologically documented Stage IV NSCLC.

          3. Confirmed tumor PD-L1 status prior to randomization.

          4. Patients must have tumors that lack activating EGFR mutations and ALK fusions.

          5. No prior chemotherapy or any other systemic therapy for metastatic NSCLC.

          6. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance
             status of 0 or 1.

          7. No prior exposure to immunemediated therapy, excluding therapeutic anticancer
             vaccines.

        Exclusion Criteria:

        Patients should not enter the study if any of the following exclusion criteria are
        fulfilled:

          1. Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant.

          2. Active or prior documented autoimmune or inflammatory disorders.

          3. Brain metastases or spinal cord compression unless the patient's condition is stable
             and off steroids.

          4. Active infection including tuberculosis, hepatitis B, hepatitis C, or human
             immunodeficiency virus.