57O Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): A phase I expansion in TKI-naïve patients (pts) with EGFR mutant NSCLC

The human IgG1 monoclonal antibody D blocks interaction of PD-L1 with PD-1 and CD-80 with high affinity and selectivity. This Phase I open-label multicentre study (NCT02088112) was initiated to evaluate D in combination with the EGFR TKI G in NSCLC. Expansion phase data are reported. The ongoing expansion phase combines D 10 mg/kg every 2 weeks plus G 250 mg once-daily in TKI naïve NSCLC pts with sensitising EGFR mutations. Arm 1 (10 pts): concurrent D plus G; Arm 2 (10 pts): 4 weeks of priming G monotherapy followed by concurrent D plus G. Primary endpoint: safety and tolerability. Secondary endpoints: tumour response (RECIST 1.1); pharmacokinetics (PK); pharmacodynamics (PD); immunogenicity. Pt demographics were similar across Arms (table). At data cut off (15 Sept 2015), follow-up was ≥3 months for all pts. G plus D combination was tolerable (most frequently reported treatment-related adverse events [AEs] of any grade: see table). Treatment-related CTC Grade 3–4 AEs led to discontinuation in 4 pts, all from Arm 2: increased ALT and/or AST (n = 3), pneumonitis (n = 1). Investigator-determined best objective response rate in 19 evaluable pts at ≥8 weeks: Arm 1 77.8% (7/9); Arm 2 80.0% (8/10) (table). No significant PK or PD interactions were observed nor anti-drug antibodies detected.Tabled 1Expansion PhaseArm 1 (N = 10)Arm 2 (N = 10)DemographicsMale, n (%)5 (50.0)5 (50.0)Median age, years (range)54.5 (27–68)66.0 (57–76)Never-smoker, n (%)4 (40.0)6 (60.0)Exon 19 deletion, n (%)6 (60.0)5 (50.0)Exon 21 L858R, n (%)4 (40.0)4 (40.0)Treatment-related AEs (occurring in ≥4 pts in any Arm)Total, naNumber of pts reporting ≥1 AE.10 (100)10 (100)Diarrhoea, n (%)8 (80.0)6 (60.0)ALT increased, n (%)7 (70.0)6 (60.0)AST increased, n (%)4 (40.0)5 (50.0)Pruritus, n (%)4 (40.0)6 (60.0)Dry skin, n (%)3 (30.0)5 (50.0)Nausea, n (%)4 (40.0)1 (10.0)Rash, n (%)6 (60.0)4 (40.0)Tumour responsebn = 19 pts with tumour data available for analysis.Arm 1Arm 2(N = 9)(N = 10)Best objective response ratecComplete + partial response., n (%)7 (77.8)8 (80.0)Complete response, n (%)1 (11.1)0 (0.0)Partial response, n (%)6 (66.7)8 (80.0)Stable disease ≥8 weeks, n (%)2 (22.2)1 (10.0)Not evaluable, n (%)0 (0.0)0 (0.0)AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; pts, patients.a Number of pts reporting ≥1 AE.b n = 19 pts with tumour data available for analysis.c Complete + partial response. Open table in a new tab AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; pts, patients. D 10 mg/kg plus G 250 mg was generally tolerated, with encouraging activity observed in TKI naïve NSCLC pts with sensitising EGFR mutations, supporting continued evaluation of this combination.