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. 2021 Apr 30;2021(4):CD013257. doi: 10.1002/14651858.CD013257.pub3

PEARL.

Study name A phase III randomized, open‐label, multi‐center study of durvalumab (MEDI4736) versus standard of care (SoC) platinum‐based chemotherapy as first line treatment in patients with PD‐L1‐High Expression advanced Non Small‐Cell Lung Cancer
Methods Open‐label, parallel assignment, Phase 3 RCT
Participants 662 participants
Inclusion criteria

  • Aged at least 18 years

  • Documented evidence of Stage IV NSCLC

  • No sensitising EGFR mutation and ALK rearrangement

  • PD‐L1 expression positive

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1


Exclusion criteria

  • Prior chemotherapy or any other systemic therapy for advanced NSCLC

  • Prior exposure to immune‐mediated therapy, including, but not limited to, other anti‐cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4), anti‐programmed cell death1 (PD‐1), anti‐programmed cell death ligand 1 (PD‐L1), or anti PD‐L2 antibodies, excluding therapeutic anticancer vaccines

  • Brain metastases or spinal cord compression unless the patient is stable and off steroids for at least 14 days prior to start of study treatment

  • Mixed small‐cell lung cancer and NSCLC histology, sarcomatoid variant

  • Active or prior documented autoimmune or inflammatory disorders (e.g., colitis or Crohn's disease]
Interventions Intervention
Durvalumab (MEDI4736)
Anti‐PD‐L1 monoclonal Antibody monotherapy
Comparator:
Standard of care: platinum‐based chemotherapy
Outcomes Primary outcome measures

  • The efficacy of Durvalumab therapy compared to SoC in terms of overall survival (OS) in patients with NSCLC (timefFrame: 4 years)


Secondary outcome measures

  • The efficacy of Durvalumab compared to SoC in terms of Objective response rate (ORR) (time frame: 4 years)

  • The efficacy of Durvalumab compared to SoC in terms of Duration of response (DoR) (time frame: 4 years)

  • The efficacy of Durvalumab compared to SoC in terms of A Proportion of patients alive and progression free at 12 months from randomisation (APF12) (time frame: 12 months)

  • The efficacy of Durvalumab compared to SoC in terms of progression‐free survival after subsequent anticancer therapy (PFS2) (time frame: 4 years)

  • Disease‐related symptoms and health‐related quality of life in participants treated with durvalumab compared to SoC using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (time frame: 4 years)

  • The immunogenicity of durvalumab by measuring the presence of Anti‐drug Antibodies (time frame: 4 years)

  • The efficacy of Durvalumab therapy compared to SoC in terms of progress‐free survival (PFS) in patients with NSCLC (time frame: 4 years)

  • The efficacy of Durvalumab therapy compared to SoC in terms of Overall Survival (OS) in PD‐L1 high patients with NSCLC (time frame: 4 years)


Other outcome measures

  • The Incidence of Treatment‐Emergent Adverse Events assessed by Common Terminology Criteria for Adverse Event (CTCAE) v4.03 for participants receiving Durvalumab therapy or SoC (time frame: 4 years)
Starting date Actual study start date: January 2, 2017
Estimated study completion date: December 31, 2020
Contact information  
Notes ClinicalTrials.gov Identifier: NCT03003962