Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor–Mutated, MET-Amplified Non–Small Cell Lung Cancer: TATTON

Ryan J. Hartmaier; Aleksandra A. Markovets; Myung Ju Ahn; Lecia V. Sequist; Ji Youn Han; Byoung Chul Cho; Helena A. Yu; Sang We Kim; James Chih Hsin Yang; Jong Seok Lee; Wu Chou Su; Dariusz M. Kowalski; Sergey Orlov; Song Ren; Paul Frewer; Xiaoling Ou; Darren A.E. Cross; Nisha Kurian; Mireille Cantarini; Pasi A. Jänne

doi:10.1158/2159-8290.CD-22-0586

Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor–Mutated, MET-Amplified Non–Small Cell Lung Cancer: TATTON

Ryan J. Hartmaier, Aleksandra A. Markovets, Myung Ju Ahn, Lecia V. Sequist, Ji Youn Han, Byoung Chul Cho, Helena A. Yu, Sang We Kim, James Chih Hsin Yang, Jong Seok Lee, Wu Chou Su, Dariusz M. Kowalski, Sergey Orlov, Song Ren, Paul Frewer, Xiaoling Ou, Darren A.E. Cross, Nisha Kurian, Mireille Cantarini, Pasi A. Jänne

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

MET-inhibitor and EGFR tyrosine kinase inhibitor (EGFR-TKI) combination therapy could overcome acquired MET-mediated osimertinib resistance. We present the final phase Ib TATTON (NCT02143466) analysis (Part B, n = 138/Part D, n = 42) assessing oral savolitinib 600 mg/300 mg once daily (q.d.) + osimertinib 80 mg q.d. in patients with MET-amplified, EGFR-mutated (EGFRm) advanced non–small cell lung cancer (NSCLC) and progression on prior EGFR-TKI. An acceptable safety profile was observed. In Parts B and D, respectively, objective response rates were 33% to 67% and 62%, and median progression-free survival (PFS) was 5.5 to 11.1 months and 9.0 months. Increased antitumor activity may occur with MET copy number ≥10. EGFRm circulating tumor DNA clearance on treatment predicted longer PFS in patients with detectable baseline ctDNA, while acquired resistance mechanisms to osimertinib + savolitinib were mediated by MET, EGFR, or KRAS alterations.

Original language	English
Pages (from-to)	98-113
Number of pages	16
Journal	Cancer Discovery
Volume	13
Issue number	1
DOIs	https://doi.org/10.1158/2159-8290.CD-22-0586
Publication status	Published - 2023 Jan 1

Bibliographical note

Funding Information:
The authors thank all the patients and their families. The study (NCT02143466) was funded by AstraZeneca, the manufacturer of the drugs savolitinib and osimertinib. The authors acknowledge Bernadette Tynan, MSc, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by Astra-Zeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Publisher Copyright:
© 2022 The Authors; Published by the American Association for Cancer Research.

All Science Journal Classification (ASJC) codes

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/2159-8290.CD-22-0586

Cite this

Hartmaier, R. J., Markovets, A. A., Ahn, M. J., Sequist, L. V., Han, J. Y., Cho, B. C., Yu, H. A., Kim, S. W., Yang, J. C. H., Lee, J. S., Su, W. C., Kowalski, D. M., Orlov, S., Ren, S., Frewer, P., Ou, X., Cross, D. A. E., Kurian, N., Cantarini, M., & Jänne, P. A. (2023). Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor–Mutated, MET-Amplified Non–Small Cell Lung Cancer: TATTON. Cancer Discovery, 13(1), 98-113. https://doi.org/10.1158/2159-8290.CD-22-0586

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title = "Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor–Mutated, MET-Amplified Non–Small Cell Lung Cancer: TATTON",

abstract = "MET-inhibitor and EGFR tyrosine kinase inhibitor (EGFR-TKI) combination therapy could overcome acquired MET-mediated osimertinib resistance. We present the final phase Ib TATTON (NCT02143466) analysis (Part B, n = 138/Part D, n = 42) assessing oral savolitinib 600 mg/300 mg once daily (q.d.) + osimertinib 80 mg q.d. in patients with MET-amplified, EGFR-mutated (EGFRm) advanced non–small cell lung cancer (NSCLC) and progression on prior EGFR-TKI. An acceptable safety profile was observed. In Parts B and D, respectively, objective response rates were 33% to 67% and 62%, and median progression-free survival (PFS) was 5.5 to 11.1 months and 9.0 months. Increased antitumor activity may occur with MET copy number ≥10. EGFRm circulating tumor DNA clearance on treatment predicted longer PFS in patients with detectable baseline ctDNA, while acquired resistance mechanisms to osimertinib + savolitinib were mediated by MET, EGFR, or KRAS alterations.",

author = "Hartmaier, {Ryan J.} and Markovets, {Aleksandra A.} and Ahn, {Myung Ju} and Sequist, {Lecia V.} and Han, {Ji Youn} and Cho, {Byoung Chul} and Yu, {Helena A.} and Kim, {Sang We} and Yang, {James Chih Hsin} and Lee, {Jong Seok} and Su, {Wu Chou} and Kowalski, {Dariusz M.} and Sergey Orlov and Song Ren and Paul Frewer and Xiaoling Ou and Cross, {Darren A.E.} and Nisha Kurian and Mireille Cantarini and J{\"a}nne, {Pasi A.}",

note = "Funding Information: The authors thank all the patients and their families. The study (NCT02143466) was funded by AstraZeneca, the manufacturer of the drugs savolitinib and osimertinib. The authors acknowledge Bernadette Tynan, MSc, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by Astra-Zeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). Publisher Copyright: {\textcopyright} 2022 The Authors; Published by the American Association for Cancer Research.",

year = "2023",

month = jan,

day = "1",

doi = "10.1158/2159-8290.CD-22-0586",

language = "English",

volume = "13",

pages = "98--113",

journal = "Cancer Discovery",

issn = "2159-8274",

publisher = "American Association for Cancer Research Inc.",

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Hartmaier, RJ, Markovets, AA, Ahn, MJ, Sequist, LV, Han, JY, Cho, BC, Yu, HA, Kim, SW, Yang, JCH, Lee, JS, Su, WC, Kowalski, DM, Orlov, S, Ren, S, Frewer, P, Ou, X, Cross, DAE, Kurian, N, Cantarini, M & Jänne, PA 2023, 'Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor–Mutated, MET-Amplified Non–Small Cell Lung Cancer: TATTON', Cancer Discovery, vol. 13, no. 1, pp. 98-113. https://doi.org/10.1158/2159-8290.CD-22-0586

TY - JOUR

T1 - Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor–Mutated, MET-Amplified Non–Small Cell Lung Cancer

T2 - TATTON

AU - Hartmaier, Ryan J.

AU - Markovets, Aleksandra A.

AU - Ahn, Myung Ju

AU - Sequist, Lecia V.

AU - Han, Ji Youn

AU - Cho, Byoung Chul

AU - Yu, Helena A.

AU - Kim, Sang We

AU - Yang, James Chih Hsin

AU - Lee, Jong Seok

AU - Su, Wu Chou

AU - Kowalski, Dariusz M.

AU - Orlov, Sergey

AU - Ren, Song

AU - Frewer, Paul

AU - Ou, Xiaoling

AU - Cross, Darren A.E.

AU - Kurian, Nisha

AU - Cantarini, Mireille

AU - Jänne, Pasi A.

N1 - Funding Information: The authors thank all the patients and their families. The study (NCT02143466) was funded by AstraZeneca, the manufacturer of the drugs savolitinib and osimertinib. The authors acknowledge Bernadette Tynan, MSc, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by Astra-Zeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). Publisher Copyright: © 2022 The Authors; Published by the American Association for Cancer Research.

PY - 2023/1/1

Y1 - 2023/1/1

N2 - MET-inhibitor and EGFR tyrosine kinase inhibitor (EGFR-TKI) combination therapy could overcome acquired MET-mediated osimertinib resistance. We present the final phase Ib TATTON (NCT02143466) analysis (Part B, n = 138/Part D, n = 42) assessing oral savolitinib 600 mg/300 mg once daily (q.d.) + osimertinib 80 mg q.d. in patients with MET-amplified, EGFR-mutated (EGFRm) advanced non–small cell lung cancer (NSCLC) and progression on prior EGFR-TKI. An acceptable safety profile was observed. In Parts B and D, respectively, objective response rates were 33% to 67% and 62%, and median progression-free survival (PFS) was 5.5 to 11.1 months and 9.0 months. Increased antitumor activity may occur with MET copy number ≥10. EGFRm circulating tumor DNA clearance on treatment predicted longer PFS in patients with detectable baseline ctDNA, while acquired resistance mechanisms to osimertinib + savolitinib were mediated by MET, EGFR, or KRAS alterations.

AB - MET-inhibitor and EGFR tyrosine kinase inhibitor (EGFR-TKI) combination therapy could overcome acquired MET-mediated osimertinib resistance. We present the final phase Ib TATTON (NCT02143466) analysis (Part B, n = 138/Part D, n = 42) assessing oral savolitinib 600 mg/300 mg once daily (q.d.) + osimertinib 80 mg q.d. in patients with MET-amplified, EGFR-mutated (EGFRm) advanced non–small cell lung cancer (NSCLC) and progression on prior EGFR-TKI. An acceptable safety profile was observed. In Parts B and D, respectively, objective response rates were 33% to 67% and 62%, and median progression-free survival (PFS) was 5.5 to 11.1 months and 9.0 months. Increased antitumor activity may occur with MET copy number ≥10. EGFRm circulating tumor DNA clearance on treatment predicted longer PFS in patients with detectable baseline ctDNA, while acquired resistance mechanisms to osimertinib + savolitinib were mediated by MET, EGFR, or KRAS alterations.

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U2 - 10.1158/2159-8290.CD-22-0586

DO - 10.1158/2159-8290.CD-22-0586

M3 - Article

C2 - 36264123

AN - SCOPUS:85144879255

SN - 2159-8274

VL - 13

SP - 98

EP - 113

JO - Cancer Discovery

JF - Cancer Discovery

IS - 1

ER -

Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor–Mutated, MET-Amplified Non–Small Cell Lung Cancer: TATTON

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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