136O - Osimertinib combined with durvalumab in EGFR-mutant non-small cell lung cancer: Results from the TATTON phase Ib trial

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 Myung-Ju Ahn
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors M. Ahn1, J.C. Yang2, H. Yu3, H. Saka4, S. Ramalingam5, K. Goto6, S. Kim7, L. Yang8, A. Walding9, G.R. Oxnard10
  • 1Department Of Medicine, Section Of Hematology-oncology, Samsung Medical Center, Sungkyunkwan University, 135-710 - Seoul/KR
  • 2Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 3Department Of Medicine, Memorial Sloan-Kettering Cancer Center, New York/US
  • 4Respiratory Medicine And Medical Oncology, Japanese National Hospital Organization, Nagoya Medical Center, Nagoya/JP
  • 5Department Of Hematology And Medical Oncology, Winship Cancer Institute of Emory University, 30322 - Atlanta/US
  • 6Department Of Thoracic Oncology, National Cancer Center East, Chiba/JP
  • 7Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 8Oncology, Global Medicine Development, AstraZeneca, Shanghai/CN
  • 9Patient Safety, AstraZeneca, Macclesfield/GB
  • 10Lowe Center For Thoracic Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US

Abstract

Background

Osimertinib (AZD9291) is a potent, irreversible EGFR-TKI selective for EGFRm and T790M resistance mutations; durvalumab is a selective, high-affinity human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Tolerability and safety of combining novel targeted therapies warrants investigation. We report updated data from the osimertinib + durvalumab (MEDI4736) arm of TATTON.

Methods

TATTON (NCT02143466) is a multi-arm Phase Ib trial conducted in two parts: dose escalation (Part A) in EGFR-TKI pre-treated pts and dose expansion (Part B) in EGFR-TKI treatment-naïve pts. Inclusion in the osimertinib + durvalumab arm required EGFR-mutant NSCLC and no contraindication for immunotherapy, and excluded pts with a history of interstitial lung disease (ILD). All pts received 80 mg osimertinib, orally, qd + durvalumab at 3 mg/kg or 10 mg/kg IV q2w (Part A) or 10 mg/kg q2w (Part B).The primary objective was safety and tolerability; secondary objectives included clinical activity.

Results

Data are preliminary and will be updated for presentation. To date, 23 and 11 pts received osimertinib + durvalumab in Part A and Part B, respectively. The most common all-causality adverse events in Part A: nausea (39%), vomiting (39%), anaemia (35%) and diarrhoea (35%); Part B: ILD (64%; grouped terms), diarrhoea (55%) and nausea (45%). ILD was reported in 6/23 pts (26%; 2 at Gr 3/4, 0 at Gr 5) in Part A and 7/11 pts (64%; 3 at Gr 3/4, 0 at Gr 5) in Part B, with no fatalities; most pts were managed with corticosteroids. Median time to ILD onset was 69 days. Of 21 evaluable pts from Part A, 12 had a partial response (PR, 9 confirmed) and 9 had stable disease (SD). Of 10 evaluable pts from Part B, 8 had a PR (7 confirmed) and 2 had SD.

Conclusions

ILD (grouped terms) have been reported in 2.9% (35/1207; 14 at Gr 3/4, 4 at Gr 5) of osimertinib and 2.0% (23/1149; 6 at Gr 3/4, 1 at Gr 5) of durvalumab monotherapy pts, compared with 38% (13/34; 5 at Gr 3/4, 0 pts at Gr 5) for the combination reported here, with no apparent increase in ILD severity. Early data suggest an encouraging clinical activity profile of osimertinib + durvalumab, while the safety profile warrants further investigation. This arm is currently on hold.

Clinical trial identification

NCT02143466 (Release date 9 May 2014)

Legal entity responsible for the study

AstraZeneca

Funding

AstraZeneca

Disclosure

M.-J. Ahn: Advisory boards: Boehringer Ingelheim, Novartis, AstraZeneca, Lilly, Merck. J. Yang: Advisory board: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, AstraZeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene. H. Yu: Research support: AstraZeneca, Clovis Oncology, Astellas, Incyte, Pfizer Advisory board: AstraZeneca. H. Saka: Study grant: AstraZeneca. S. Ramalingam: Consultancy fees: AstraZeneca, Boehringer Ingelheim, Celgene, Genentech, Novartis, Lilly, Merck, Bristol-Myers Squibb. K. Goto: Lecture fees, advisory board membership and corporate-sponsored research: AstraZeneca. L. Yang: Employee: AstraZeneca. G.R. Oxnard: Advisory board/consulting: AstraZeneca, Boehringer-Ingelheim, Clovis, Genentech, Sysmex. A. Walding: Employee and shareholder: AstraZeneca. All other authors have declared no conflicts of interest.