57O - Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with ge...

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session ESMO-IASLC Best Abstracts: The evolving landscape of immunotherapy
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Don Gibbons
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors D.L. Gibbons1, L.Q. Chow2, D. Kim3, S. Kim4, T. Yeh5, X. Song6, H. Jiang7, R. Taylor8, J. Karakunnel6, B. Creelan9
  • 1Department Of Thoracic/head And Neck Medical Oncology, Division Of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2Department Of Medicine, University of Washington, Division of Oncology, Seattle/US
  • 3Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 4Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 5Oncology Imed Translational Sciences, AstraZeneca, 02451 - Waltham/US
  • 6Oncology Clinical Development, MedImmune, Gaithersburg/US
  • 7Oncology, AstraZeneca, Shanghai/CN
  • 8Oncology, AstraZeneca, Macclesfield/GB
  • 9Department Of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, FL 33612 - Tampa/US

Abstract

Background

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.

Methods

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.

Results

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.

Expansion Phase
Arm 1 (N = 10) Arm 2 (N = 10)
Demographics
Male, 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, na 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 responseb Arm 1 (N = 9) Arm 2 (N = 10)
Best objective response rate c, 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.

Conclusions

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.

Clinical trial identification

NCT02088112

Legal entity responsible for the study

MedImmune, the global biologics R&D arm of AstraZeneca

Funding

MedImmune, the global biologics R&D arm of AstraZeneca

Disclosure

D.L. Gibbons: Stock ownership in AstraZeneca. L.Q. Chow: Research: Eli Lilly/Imclone, OSI Pharmaceuticals, BMS, Genetech, VentiRx, Pfizer, GSK, Merck, AstraZeneca/Medimmune, Novartis (paid to University of Washington); Honoraria: Astellas Pharma; Consultancy: Novartis, BMS, Merck Travel: Novartis, Merck. D.-W. Kim: Consultancy: Novartis. T. Yeh: Employee of AstraZeneca. X. Song, J. Karakunnel: Employee of Medimmune and also holds shares in Medimmune. H. Jiang: Employee of AstraZeneca and also holds shares in AstraZeneca. R. Taylor: Contractor to AstraZeneca. B. Creelan: Research Funding from Boehringer Ingelheim Travel costs from Celgene. All other authors have declared no conflicts of interest.