Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: The viktory umbrella trial

Jeeyun Lee; Seung Tae Kim; Kyung Kim; Hyuk Lee; Iwanka Kozarewa; Peter G.S. Mortimer; Justin I. Odegaard; Elizabeth A. Harrington; Juyoung Lee; Taehyang Lee; Sung Yong Oh; Jung Hun Kang; Jung Hoon Kim; Youjin Kim; Jun Ho Ji; Young Saing Kim; Kyoung Eun Lee; Jinchul Kim; Tae Sung Sohn; Ji Yeong An; Min Gew Choi; Jun Ho Lee; Jae Moon Bae; Sung Kim; Jae J. Kim; Yang Won Min; Byung Hoon Min; Nayoung K.D. Kim; Sally Luke; Young Hwa Kim; Jung Yong Hong; Se Hoon Park; Joon Oh Park; Young Suk Park; Ho Yeong Lim; Amirali Talasaz; Simon J. Hollingsworth; Kyoung Mee Kim; Won Ki Kang

doi:10.1158/2159-8290.CD-19-0442

Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: The viktory umbrella trial

Jeeyun Lee, Seung Tae Kim, Kyung Kim, Hyuk Lee, Iwanka Kozarewa, Peter G.S. Mortimer, Justin I. Odegaard, Elizabeth A. Harrington, Juyoung Lee, Taehyang Lee, Sung Yong Oh, Jung Hun Kang, Jung Hoon Kim, Youjin Kim, Jun Ho Ji, Young Saing Kim, Kyoung Eun Lee, Jinchul Kim, Tae Sung Sohn, Ji Yeong AnMin Gew Choi, Jun Ho Lee, Jae Moon Bae, Sung Kim, Jae J. Kim, Yang Won Min, Byung Hoon Min, Nayoung K.D. Kim, Sally Luke, Young Hwa Kim, Jung Yong Hong, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Amirali Talasaz, Simon J. Hollingsworth, Kyoung Mee Kim, Won Ki Kang

Department of Internal Medicine

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

183 Scopus citations

Abstract

The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RIC-TOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), ada-vosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib. SIGNIFICANCE: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility.

Original language	English
Pages (from-to)	1388-1405
Number of pages	18
Journal	Cancer Discovery
Volume	9
Issue number	10
DOIs	https://doi.org/10.1158/2159-8290.CD-19-0442
State	Published - Oct 2019

Bibliographical note

Publisher Copyright:
© 2019 American Association for Cancer Research.

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Lee, J., Kim, S. T., Kim, K., Lee, H., Kozarewa, I., Mortimer, P. G. S., Odegaard, J. I., Harrington, E. A., Lee, J., Lee, T., Oh, S. Y., Kang, J. H., Kim, J. H., Kim, Y., Ji, J. H., Kim, Y. S., Lee, K. E., Kim, J., Sohn, T. S., ... Kang, W. K. (2019). Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: The viktory umbrella trial. Cancer Discovery, 9(10), 1388-1405. https://doi.org/10.1158/2159-8290.CD-19-0442

@article{2a72ca8d43fa44309cfbd0760717683d,

title = "Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: The viktory umbrella trial",

abstract = "The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RIC-TOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), ada-vosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib. SIGNIFICANCE: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility.",

author = "Jeeyun Lee and Kim, {Seung Tae} and Kyung Kim and Hyuk Lee and Iwanka Kozarewa and Mortimer, {Peter G.S.} and Odegaard, {Justin I.} and Harrington, {Elizabeth A.} and Juyoung Lee and Taehyang Lee and Oh, {Sung Yong} and Kang, {Jung Hun} and Kim, {Jung Hoon} and Youjin Kim and Ji, {Jun Ho} and Kim, {Young Saing} and Lee, {Kyoung Eun} and Jinchul Kim and Sohn, {Tae Sung} and An, {Ji Yeong} and Choi, {Min Gew} and Lee, {Jun Ho} and Bae, {Jae Moon} and Sung Kim and Kim, {Jae J.} and Min, {Yang Won} and Min, {Byung Hoon} and Kim, {Nayoung K.D.} and Sally Luke and Kim, {Young Hwa} and Hong, {Jung Yong} and Park, {Se Hoon} and Park, {Joon Oh} and Park, {Young Suk} and Lim, {Ho Yeong} and Amirali Talasaz and Hollingsworth, {Simon J.} and Kim, {Kyoung Mee} and Kang, {Won Ki}",

note = "Publisher Copyright: {\textcopyright} 2019 American Association for Cancer Research.",

year = "2019",

month = oct,

doi = "10.1158/2159-8290.CD-19-0442",

language = "English",

volume = "9",

pages = "1388--1405",

journal = "Cancer Discovery",

issn = "2159-8274",

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

number = "10",

}

Lee, J, Kim, ST, Kim, K, Lee, H, Kozarewa, I, Mortimer, PGS, Odegaard, JI, Harrington, EA, Lee, J, Lee, T, Oh, SY, Kang, JH, Kim, JH, Kim, Y, Ji, JH, Kim, YS, Lee, KE, Kim, J, Sohn, TS, An, JY, Choi, MG, Lee, JH, Bae, JM, Kim, S, Kim, JJ, Min, YW, Min, BH, Kim, NKD, Luke, S, Kim, YH, Hong, JY, Park, SH, Park, JO, Park, YS, Lim, HY, Talasaz, A, Hollingsworth, SJ, Kim, KM & Kang, WK 2019, 'Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: The viktory umbrella trial', Cancer Discovery, vol. 9, no. 10, pp. 1388-1405. https://doi.org/10.1158/2159-8290.CD-19-0442

TY - JOUR

T1 - Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment

T2 - The viktory umbrella trial

AU - Lee, Jeeyun

AU - Kim, Seung Tae

AU - Kim, Kyung

AU - Lee, Hyuk

AU - Kozarewa, Iwanka

AU - Mortimer, Peter G.S.

AU - Odegaard, Justin I.

AU - Harrington, Elizabeth A.

AU - Lee, Juyoung

AU - Lee, Taehyang

AU - Oh, Sung Yong

AU - Kang, Jung Hun

AU - Kim, Jung Hoon

AU - Kim, Youjin

AU - Ji, Jun Ho

AU - Kim, Young Saing

AU - Lee, Kyoung Eun

AU - Kim, Jinchul

AU - Sohn, Tae Sung

AU - An, Ji Yeong

AU - Choi, Min Gew

AU - Lee, Jun Ho

AU - Bae, Jae Moon

AU - Kim, Sung

AU - Kim, Jae J.

AU - Min, Yang Won

AU - Min, Byung Hoon

AU - Kim, Nayoung K.D.

AU - Luke, Sally

AU - Kim, Young Hwa

AU - Hong, Jung Yong

AU - Park, Se Hoon

AU - Park, Joon Oh

AU - Park, Young Suk

AU - Lim, Ho Yeong

AU - Talasaz, Amirali

AU - Hollingsworth, Simon J.

AU - Kim, Kyoung Mee

AU - Kang, Won Ki

PY - 2019/10

Y1 - 2019/10

N2 - The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RIC-TOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), ada-vosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib. SIGNIFICANCE: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility.

AB - The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RIC-TOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), ada-vosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib. SIGNIFICANCE: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility.

UR - http://www.scopus.com/inward/record.url?scp=85072849104&partnerID=8YFLogxK

U2 - 10.1158/2159-8290.CD-19-0442

DO - 10.1158/2159-8290.CD-19-0442

M3 - Article

C2 - 31315834

AN - SCOPUS:85072849104

SN - 2159-8274

VL - 9

SP - 1388

EP - 1405

JO - Cancer Discovery

JF - Cancer Discovery

IS - 10

ER -

Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: The viktory umbrella trial

Abstract

Bibliographical note

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