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성균관대학교 의과대학

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J. Thorac. Oncol., Volume 11, Issue 4, Supplement, April 2016, Page S115 | https://doi.org/10.1016/S1556-0864(16)30246-5 136O: Osimertinib combined with durvalumab in EGFR-mutant non-small cell lung cancer: Results from the TATTON phase Ib trial

M.-J. Ahn^a, J. Yang^b, H. Yu^c, H. Saka^d, S. Ramalingam^e, K. Goto^f, S.-W. Kim^g, L. Yang^h, A. Waldingⁱ, G.R. Oxnard^j

^aDepartment of Medicine, Section of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
^bDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan
^cDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
^dRespiratory Medicine and Medical Oncology, Japanese National Hospital Organization, Nagoya Medical Center, Nagoya, Japan
^eDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
^fDepartment of Thoracic Oncology, National Cancer Center East, Chiba, Japan
^gDepartment of Oncology, Asan Medical Center, University of Ulsan School of Medicine, Seoul, Republic of Korea
^hOncology, Global Medicine Development, AstraZeneca, Shanghai, China
ⁱPatient Safety, AstraZeneca, Macclesfield, UK
^jLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

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 pretreated 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.

논문정보

형식Research article
게재일2016년 04월 (BRIC 등록일 2020-07-13)
연구진국내+국외 연구진
분야 의약학 > 종양의학
피인용횟수120회 이상 인용된 논문

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