High PD-L1 expression in lung tumors is associated with response to PD-L1-targeted treatment. Durvalumab, an anti-PD-L1 monoclonal antibody, was evaluated in patients with advanced solid tumors, including NSCLC, in a Phase 1/2 multicenter, open-label study (NCT01693562).
Patients received durvalumab 10 mg/kg IV Q2W for up to 12 months or until unacceptable toxicity or disease progression. Safety was evaluated (CTCAE v4.03) through 90 days after last dose; confirmed response (RECIST v1.1) was based on investigator assessment. Retreatment was permitted only upon progression after 12 months of therapy in patients with disease control. Tumor PD-L1 expression was assessed using the Ventana PD-L1 IHC (SP263) assay.
As of 29 April 2016, 304 NSCLC patients received durvalumab; 144 (47%) had non-squamous and 160 (53%) had squamous histology; median age was 65 years (range 26–87 years); ECOG performance status was 0 in 24% and 1 in 76%; and 85% were current/prior smokers. Median number of doses was 6 (range 1–27). Any-grade drug-related AEs were reported in 57% of patients, most frequently fatigue (17%), decreased appetite (9%), and diarrhea (9%). Drug-related AEs were Grade ≥3 in 10% of patients; most common were fatigue, hyponatremia, and colitis (each 1%). Any-grade drug-related AEs led to study drug discontinuation in 5% of patients. Pneumonitis Grade 1–2 occurred in 5 (2%) patients and Grade 4 in 1 (
The safety profile of durvalumab in NSCLC is manageable and consistent with previous reports. Patients with tumors defined as PD-L1 positive had improved ORR and OS.
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S.J. Antonia: Consulting/Advisory: BMS, AZ, Merck. J.R. Brahmer: Consulting/Advisory: AZ/Medimmune Research funding: AZ/Medimmune. S. Khleif: Leader/stock: Advaxis Honor: MEDI, AZ, NewLink, Advaxis, Lucena, PDS Consult/AB: Gilead, Janssen, Nektan, Merus, GHI, BI Res fund: MEDI, AZ, NewLink, Advaxis, PDS, Serono, IOBiotech, Caretech, Medivation Travel: MEDI, AZ, NewLink, Advaxis, Lucena. A.S. Balmanoukian: Speaker Bureau: BMS, Merck Research funding: Medimmune, Genentech, BMS, Merck Serono. S-H.I. Ou: Consulting/advisory: ARIAD, Pfizer, Roche, AZ Speaker Bureau: Roche, AZ, BI Research funding: ARIAD, AZ, BI< Pfizer, Igyta, Daiichi Sankyo, Clovis. M. Gutierrez: Employment: Hackensack University Medical Center Other relationship: Speaker Bureau Merck/BMS. M-J. Ahn: Honoraria: MSD, BMS, AZ, BI, Novartis Consulting/Advisory: BI, BMS, AZ, MSD, Novartis Research funding: AZ. R. Jamal: Honoraria: BMS, Merck Consulting advisory: BMS, Merck Research funding: BMS, Merck. D. Jaeger: Consulting/Advisory: Roche, BMS, Bayer, Definiens. G. Jerusalem: Honoraria: Novartis, Roche, Celgene Consulting or advisory: Novartis, Roche, Celgene, Amgen, Pfizer Research funding: Novartis, Roche, MSD Travel, accommodations, expenses: Novartis, Roche, GSK. X. Jin: Employment: Unitech Heal Care, Medimmune Stock/other ownership: AZ, United Health group. A. Gupta: Employment: Medimmune Stock/ownership: BMS, AZ Patents, royalties, IP: BMS. J. Antal: Employment: Medimmune Stock/ownership: AZ, GSK. N.H. Segal: Consultancy: Medimmune/AZ, BMS, Roche, Pfizer Research funding: Medimmune/AZ, BMS. All other authors have declared no conflicts of interest.