Presented on: ESMO, October 19-23, 2018, Munich, Germany

EXPLORATORY ANALYSES OF OVERALL SURVIVAL IN PACIFIC

Corinne Faivre-Finn,1 David R. Spigel,2 Suresh Senan,3 Corey J.Langer,4 David Raben,5 Bradford Perez,6 Mustafa Özgüroğlu,7 Davey Daniel,8 Augusto Villegas,9 David Vicente,10 Rina Hui,11 Shuji Murakami,12 Luis Paz-Ares,13

Lynne Poole,14 Catherine Wadsworth,15 Phillip A. Dennis,16 Scott J. Antonia6

1The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK; 2Sarah Cannon Research Institute, Nashville, TN, USA; 3VU University Medical Center, Amsterdam, The Netherlands; 4University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 5University of Colorado Cancer Center, Aurora, CD, USA; 6H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA;7Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey; 8Tennessee Oncology, Chattanooga, TN, and Sarah Cannon ResearchInstitute, Nashville, TN, USA; 9Cancer Specialists of North Florida, Jacksonville, FL, USA; 10Hospital Universitario Virgen Macarena, Seville, Spain; 11Westmead Hospital and the University of Sydney, Sydney, NSW, Australia; 12Kanagawa Cancer Center, Yokohama, Japan; 13Hospital Universitario 12 de Octubre, CiberOnc, Universidad Complutense and CNIO, Madrid, Spain; 14AstraZeneca, Cambridge, UK; 15AstraZeneca, Alderley Park, UK; 16AstraZeneca, Gaithersburg, MD, USA

PACIFIC: study design

Presented on: ESMO, October 19-23, 2018, Munich, Germany

R

*Using the Ventana PD-L1 (SP263) assay; ↑defined as the time from randomisation until the date of objective disease progression or death by any cause in the absence of progression

BICR, blinded independent central review; cCRT, concurrent CRT; DoR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PFS2, time to second progression; PRO, patient-reported outcome; q2w, every 2 weeks; RECIST, Response Evaluation Criteria in Solid Tumors; TTDM, time to death or distant metastasis; WHO PS, World Health Organization performance status

Antonia SJ, et al. N Engl J Med 2017;377:1919-29ClinicalTrials.gov number: NCT02125461

Phase 3, randomised, double-blind, placebo-controlled, multicentre, international study1

Durvalumab10 mg/kg q2w for up to 12 months

N=476

Placeboq2w for up to 12 months

N=237

Stratified by age, sex and smoking history

N=713 randomised

2:1 randomisation

• Unresectable, Stage III NSCLC without progression afterdefinitive platinum-based cCRT(≥2 cycles)

• 18 years or older

• WHO PS score 0 or 1

• If available, archived pre-cCRTtumour tissue for PD-L1 testing*

All-comers population(i.e. irrespective of PD-L1 status)

1-42 dayspost cCRT

Primary endpoints• PFS by BICR using

RECIST v1. 1†

• OS

Key secondaryendpoints• ORR, DoR and TTDM

by BICR• PFS2 by investigator• Safety• PROs

PACIFIC: PFS and OS in the ITT population

Presented on: ESMO, October 19-23, 2018, Munich, Germany

1. Antonia SJ, et al. N Engl J Med 2017;377:1919-29;2. Antonia SJ, et al. N Engl J Med. 2018; Epub Sep 25PFS DCO: 13 February 2017; OS DCO: 22 March 2018

*Median duration of follow-up was 25.2 months (range 0.2-43.1); †adjusted for interim analysisCl, confidence interval; HR, hazard ratio; ITT, intention-to-treat; NR, not reached

Improvement in PFS by PD-L1 TC ≥1% and <1%

Presented on: ESMO, October 19-23, 2018, Munich, Germany

PFS DCO: 13 February 2017; OS DCO: 22 March 2018

mo, months; NR, not reached; TC, tumour cell

OS by PD-L1 TC ≥1% and <1%

Presented on: ESMO, October 19-23, 2018, Munich, Germany

PFS DCO: 13 February 2017; OS DCO: 22 March 2018

• In the PD-L1 TC <1% subgroup, the number of events are low and overall the subgroup is small

• Imbalances in baseline characteristics

RMST, restricted mean survival time

Summary of PD-L1 analyses

Presented on: ESMO, October 19-23, 2018, Munich, Germany

• PACIFIC was designed to evaluate durvalumab in the ITT (all-comers) population

• PD-L1 testing was not mandatory and status was unknown for 37% of patients

• Safety outcomes were similar regardless of PD-L1 status

• Definitive conclusions on outcomes by PD-L1 status cannot be drawndue to limitations around post-hoc exploratory subgroup analyses

Conclusions

Presented on: ESMO, October 19-23, 2018, Munich, Germany

• PACIFIC study was designed to evaluate the benefit of durvalumab in an all-comers population

• Post-hoc exploratory subgroup analyses have shown

– For PD-L1 by TC 1% subgroups• ≥1% subgroup – PFS and OS improvement

• <1% subgroup – PFS benefit, OS confounded by performance of placebo arm

• Similar safety across all PD-L1 subgroups

– Improved PFS and OS with durvalumab regardless of type of chemotherapy, radiation doseused or time from radiation to randomisation

– These analyses have known limitations that preclude definitive conclusions

• These data support the PACIFIC regimen of durvalumab following CRT as the new standard of care in the treatment of patients with unresectable, Stage III NSCLC

PFS DCO: 13 February 2017; OS DCO: 22 March 2018