NSCLC is highly prevalent in Asia. Differences in outcomes to therapy, including longer survival and higher response rates, have been noted in Asian vs Caucasian NSCLC patients due to the higher prevalence of targetable oncogenes (i.e. EGFR sensitizing mutation or ALK translocation) in the Asian population. Until recently, standard of care (SoC) first-line treatment of EGFR/ALK wild-type advanced NSCLC comprised systemic platinum-based doublets. However, over recent years, immune checkpoint blockade has also become an important option, including in the first-line setting where pembrolizumab is approved in the US, EU and Japan in patients whose tumours express high levels of PD-L1. Durvalumab is a selective, high-affinity, anti-PD-L1 antibody that has shown antitumour activity and manageable tolerability across multiple tumour types, including NSCLC. The PEARL study aims to assess first-line durvalumab vs SoC in predominantly Asian populations with EGFR/ALK wild-type advanced NSCLC and high tumour PD-L1 expression.
PEARL (NCT03003962) is a randomised, open-label, multicentre Phase 3 study. Eligible patients are immunotherapy- and chemotherapy-naïve with Stage IV, EGFR/ALK wild-type NSCLC, high PD-L1 expression (≥25% tumour cells with membrane staining using the Ventana PD-L1 [SP263] Assay) and ECOG performance status of 0 or 1. ∼440 patients will be stratified by level of PD-L1 expression, histology and smoking status, and randomised 1:1 to receive either durvalumab (20 mg/kg i.v. every 4 weeks [q4w]) or SoC platinum-based chemotherapy until disease progression. The co-primary endpoints are PFS using blinded independent central review assessments according to RECIST v1.1 and OS. Secondary endpoints include ORR; duration of response; proportion of patients alive and progression free at 12 months; PFS after subsequent anticancer therapy; disease-related symptoms and HRQoL; immunogenicity; safety (CTCAE v4.03) and tolerability. Tumour assessments will be performed q6w for the first 48 weeks and then q8w as defined by RECIST v1.1 until confirmed disease progression. Recruitment is ongoing in Australia, China, Republic of Korea, Russia, Thailand and Vietnam.
Clinical trial identification
NCT03003962 (release date: December 15, 2016)
Legal entity responsible for the study
Y-L. Wu: Speaker fees: Roche, AstraZeneca, Eli Lilly, Sanofi, Pfizer. S. Lu: Speakers\' Bureau: AstraZeneca, Eli Lilly, Roche, Sanofi Corporate sponsored research: AstraZeneca, Boehringer-Ingelheim, Hutchison, Roche Consultant: AstraZeneca, Boehringer-Ingelheim, Hutchison, MediPharma, Roche. S. Clarke: Corporate sponsored research: Ipsen, Merck Honoraria: AstraZeneca, Ipsen, Merck. K. Lactionov: Consultant BMS, AstraZeneca, MSD, Pfizer and travel grants BMS, AstraZeneca, MSD, Pfizer P. Li, M. Kirkby, P. Stockman: AstraZeneca: full-time employment and stock ownership. Y. Xie: AstraZeneca: full-time employment.