82O - Durvalumab in ≥ 3rd-line EGFR mutant/ALK+, locally advanced or metastatic NSCLC: Results from the phase 2 ATLANTIC study

Date 07 May 2017
Event ELCC 2017
Session ESMO-IASLC Best Abstracts
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Marina Garassino
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors M. Garassino1, B. Cho2, J.E. Gray3, J. Mazières4, K. Park5, R.A. Soo6, P. Dennis7, Y. Huang7, C. Wadsworth8, N. Rizvi9
  • 1Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2Yonsei University College Of Medicine, Yonsei Cancer Center, 120-752 - Seoul/KR
  • 3H. Lee Moffitt Cancer Center and Research Institute, 33612 - Tampa/US
  • 4CHU de Toulouse - Hôpital Larrey, 31059 - Toulouse/FR
  • 5Samsung Medical Center, 6351 - Seoul/KR
  • 6National University Hospital, 119228 - Singapore/SG
  • 7AstraZeneca, 20878 - Gaithersburg/US
  • 8AstraZeneca, SK10 4TF - Alderley Park/GB
  • 9Columbia University Medical Center, 10032 - New York/US

Abstract

Background

Anti-PD-1/PD-L1 therapies have demonstrated meaningful clinical benefit in pts with EGFR/ALK wild-type (WT) advanced NSCLC. However, to our knowledge these agents have never been investigated in a study prospectively focusing on NSCLC pts with EGFR mutations or ALK alterations (EGFRmut/ALK+), a distinct subgroup with clear biological and treatment outcome differences compared with EGFR/ALK WT pts. Durvalumab is an engineered human IgG1 mAb targeting PD-L1.

Methods

ATLANTIC (NCT02087423) was a Phase 2, open-label, single-arm trial in pts with locally advanced or metastatic Stage IIIB–IV NSCLC (WHO PS 0 or 1; ≥2 prior systemic regimens, including 1 platinum-based and 1 TKI [EGFRmut/ALK+ pts]). There was no maximum number of prior treatments. The study initially enrolled all-comers and then was restricted to pts with PD-L1 high tumours (≥25% of tumour cells with membrane staining). The study included 3 pt cohorts defined by EGFR/ALK status and tumor PD-L1 expression; here we report results from EGFRmut/ALK+ pts (Cohort 1). The primary outcome was ORR (RECIST v1.1). Secondary outcomes included DCR, DoR, PFS, OS, and safety (CTCAE v4.03).

Results

As of 3 June 2016, 111 pts (median age 61 years, 63% female, 59% WHO PS 1, 99% non-squamous histology; 59% never smokers; mean prior therapies 3.8) had received durvalumab (10 mg/kg i.v. q2w for ≤12 months). Responses were durable. Most AEs were low grade. Immune-mediated AEs were manageable with standard treatment guidelines; 5.4% of pts had Grade ≥3 treatment-related (TR) AEs and 0.9% had TRAEs leading to discontinuation.rnTable: 82Orn

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
rnPD-L1 high (≥25%)PD-L1 low/negative (<25%)
n = 74an = 28a
ORR,b % (95% CI)12.2 (5.7, 21.8)3.6 (0.1, 18.3)
DCR, % (95% CI)20.3 (11.8, 31.2)7.1 (0.9, 23.5)
mDoR, months (95% CI)7.4 (5.4, 9.2)NCc
rnn = 77dn = 30d
mPFS, months (95% CI)1.9 (1.8, 3.6)1.9 (1.8, 1.9)
mOS, months (95% CI)13.3 (8.1, NC)9.9 (4.2, 13.0)
1-year OS, % (95% CI)54.8 (41.5, 66.3)40.0 (22.1, 57.4)
mFollow-up for OS, months6.58.2
rn

Note: 4 patients had PD-L1 expression unknown or missing.

rna

Full analysis set - evaluable for response per independent central review (ICR).

rnb

Confirmed response per ICR.

rnc

Not calculated due to small number of responders.

rnd

Full analysis set.

rn

DCR=disease control rate (complete response, partial response or stable disease ≥24 weeks); DoR=duration of response; m=median; NC=not calculated; ORR=objective response rate; OS=overall survival; PFS=progression-free survival

rn

Conclusions

Although the ORR was somewhat lower compared with that reported in Cohort 2 (EGFR/ALK WT), durable responses were still observed in this heavily pretreated metastatic EGFRmut/ALK+ NSCLC population. However, the data were limited by the short duration of follow up and further confirmation is needed. Activity was greater for pts with high PD-L1 expression. The tolerability profile was manageable.

Clinical trial identification

NCT02087423 (March 4, 2014)

Legal entity responsible for the study

AstraZeneca PLC

Funding

AstraZeneca

Disclosure

M.C. Garassino: Grants/research support: Pfizer; Consultant: Eli Lilly; AZ, BMS, MSD, Roche, Celgene. B-C. Cho: Grants/Research: AZ, BI, Yuhan, Roche, MSD, BMS Ono, Eli Lilly, Pfizer, Bayer Consultant: AZ, BI, Yuhan, Roche, MSD, BMS Ono, Eli Lilly, Pfizer Honoraria: AZ, BI, Yuhan, Roche, MSD, BMS Ono, Eli Lilly, Pfizer. J. Mazières: Advisory board: AZ. K. Park: Advisory role: Astellas, AZ, BI, Clovis, Lilly, Hanmi, AZ, Kyowa Hakko Kirin, Novartis, Ono, Roche Speaker bureau: BI Research: AZ. R.A. Soo: Grants/research support: AZ Honoraria: AZ, BI, BMS, Lilly, Pfizer, Roche, Taiho, Novartis, Merck. P. Dennis, Y. Huang: Employment: AZ. C. Wadsworth: Employment: AZ; Stock ownership: AZ. N. Rizvi: Consulting: AZ, Roche, Novartis, Merck, Pfizer, Lilly, AZ, BMS, Merck Stock ownership: Gritstone Oncology. All other authors have declared no conflicts of interest.