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Conference Paper: Activity of brigatinib (BRG) in crizotinib (CRZ) resistant patients (pts) according to ALK mutation status

TitleActivity of brigatinib (BRG) in crizotinib (CRZ) resistant patients (pts) according to ALK mutation status
Authors
Issue Date2016
PublisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/
Citation
52nd Annual Meeting of American Society of Clinical Oncology (ASCO 2016), Chicago, USA, 3-7 June 2016. In Journal of Clinical Oncology, 2016, v. 34 n. 15, Suppl., p. Abstract # 9060 How to Cite?
AbstractBackground: BRG is an investigational, selective ALK inhibitor with potent preclinical activity against native ALK and a broad set of mutants associated with clinical resistance to CRZ. BRG has shown promising efficacy in ALK rearranged (+) NSCLC pts previously treated with CRZ in a phase (Ph) 1/2 trial. We examined the association between BRG efficacy and ALK mutation status using tumor specimens collected after CRZ and prior to BRG treatment (tx) (baseline [BL]), and after BRG tx (Post-BL) in pts enrolled in the Ph1/2 trial and a Ph2 trial of ALK+ NSCLC pts whose disease progressed on CRZ (ALTA). Methods: Samples analysis: FoundationOne next-generation sequencing (NGS) platform. BRG activity: best response (RECIST v1.1) from BL. Data reported: Jan, 2016 for sample analyses, Nov and Dec, 2015 for Ph1/2 and ALTA clinical results, respectively. Results: Of the 301 ALK+ NSCLC pts enrolled in the Ph1/2 (N = 79) and ALTA (N = 222) trials, evaluable tumor samples were obtained from 30 pts at BL. Confirmed overall response in these pts was 63% (19/30). Secondary ALK mutations were detected in 30% (9/30) of pts. Confirmed ORR in these pts was 67% (6/9); 6 confirmed partial responses (PRs) (3 F1174L, L1196M, S1206F, and G1269A); 1 PR (G1202R) awaiting confirmation; 1 stable disease (SD) (L1196M) in a pt with 1 cycle (C = 28 days) of tx; 1 progressive disease (PD) (F1245V). Secondary ALK mutations were not detected in 70% (21/30) of pts, including 4 who were ALK fusion (-) by NGS (but ALK+ locally). Confirmed ORR in these pts was 62% (13/21); 2 CR, 11 PR, 7 SD, and 1 PD; including 3 SD and 1 PD in ALK (-) pts. Post-BL samples were collected from 5 pts (all Ph1/2), 2 of whom also had BL samples. Secondary ALK mutations, and other genetic aberrations of interest, were detected in 4 pts: 1 with F1174L (at C13 [also present at BL]; PD at C13); 2 with G1202R (at C21 [not present at BL]; PD at C13; and at C35 [BRAF G469A also detected]; PD at C35); and 1 with D1203N, G1269A, and I1171H (at C9; PD at C7). Conclusions: BRG maintains activity in CRZ resistant ALK+ NSCLC independent of the presence of secondary ALK mutations. While 2 single mutants (F1174L and G1202R) have been detected after long term tx with BRG, responses were also observed when these mutants were present at BL. Clinical trial information: NCT01449461 and NCT02094573.
DescriptionLung Cancer—Non-Small Cell Metastatic
Persistent Identifierhttp://hdl.handle.net/10722/242368
ISSN
2019 Impact Factor: 32.956
2015 SCImago Journal Rankings: 9.204

 

DC FieldValueLanguage
dc.contributor.authorGettinger, SN-
dc.contributor.authorZhang, S-
dc.contributor.authorGraeme Hodgson, J-
dc.contributor.authorBazhenova, LA-
dc.contributor.authorBurgers, S-
dc.contributor.authorKim, DW-
dc.contributor.authorTan, DS-
dc.contributor.authorKoh, HA-
dc.contributor.authorHo, JCM-
dc.contributor.authorRamirez, SV-
dc.contributor.authorShaw, AT-
dc.contributor.authorWeiss, GJ-
dc.contributor.authorLanger, CJ-
dc.contributor.authorHuber, RM-
dc.contributor.authorAhn, MJ-
dc.contributor.authorReichmann, WM-
dc.contributor.authorKerstein, D-
dc.contributor.authorRivera, VM-
dc.contributor.authorCamidge, DR-
dc.date.accessioned2017-07-24T01:38:50Z-
dc.date.available2017-07-24T01:38:50Z-
dc.date.issued2016-
dc.identifier.citation52nd Annual Meeting of American Society of Clinical Oncology (ASCO 2016), Chicago, USA, 3-7 June 2016. In Journal of Clinical Oncology, 2016, v. 34 n. 15, Suppl., p. Abstract # 9060-
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/242368-
dc.descriptionLung Cancer—Non-Small Cell Metastatic-
dc.description.abstractBackground: BRG is an investigational, selective ALK inhibitor with potent preclinical activity against native ALK and a broad set of mutants associated with clinical resistance to CRZ. BRG has shown promising efficacy in ALK rearranged (+) NSCLC pts previously treated with CRZ in a phase (Ph) 1/2 trial. We examined the association between BRG efficacy and ALK mutation status using tumor specimens collected after CRZ and prior to BRG treatment (tx) (baseline [BL]), and after BRG tx (Post-BL) in pts enrolled in the Ph1/2 trial and a Ph2 trial of ALK+ NSCLC pts whose disease progressed on CRZ (ALTA). Methods: Samples analysis: FoundationOne next-generation sequencing (NGS) platform. BRG activity: best response (RECIST v1.1) from BL. Data reported: Jan, 2016 for sample analyses, Nov and Dec, 2015 for Ph1/2 and ALTA clinical results, respectively. Results: Of the 301 ALK+ NSCLC pts enrolled in the Ph1/2 (N = 79) and ALTA (N = 222) trials, evaluable tumor samples were obtained from 30 pts at BL. Confirmed overall response in these pts was 63% (19/30). Secondary ALK mutations were detected in 30% (9/30) of pts. Confirmed ORR in these pts was 67% (6/9); 6 confirmed partial responses (PRs) (3 F1174L, L1196M, S1206F, and G1269A); 1 PR (G1202R) awaiting confirmation; 1 stable disease (SD) (L1196M) in a pt with 1 cycle (C = 28 days) of tx; 1 progressive disease (PD) (F1245V). Secondary ALK mutations were not detected in 70% (21/30) of pts, including 4 who were ALK fusion (-) by NGS (but ALK+ locally). Confirmed ORR in these pts was 62% (13/21); 2 CR, 11 PR, 7 SD, and 1 PD; including 3 SD and 1 PD in ALK (-) pts. Post-BL samples were collected from 5 pts (all Ph1/2), 2 of whom also had BL samples. Secondary ALK mutations, and other genetic aberrations of interest, were detected in 4 pts: 1 with F1174L (at C13 [also present at BL]; PD at C13); 2 with G1202R (at C21 [not present at BL]; PD at C13; and at C35 [BRAF G469A also detected]; PD at C35); and 1 with D1203N, G1269A, and I1171H (at C9; PD at C7). Conclusions: BRG maintains activity in CRZ resistant ALK+ NSCLC independent of the presence of secondary ALK mutations. While 2 single mutants (F1174L and G1202R) have been detected after long term tx with BRG, responses were also observed when these mutants were present at BL. Clinical trial information: NCT01449461 and NCT02094573.-
dc.languageeng-
dc.publisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/-
dc.relation.ispartofJournal of Clinical Oncology-
dc.titleActivity of brigatinib (BRG) in crizotinib (CRZ) resistant patients (pts) according to ALK mutation status-
dc.typeConference_Paper-
dc.identifier.emailHo, JCM: jhocm@hku.hk-
dc.identifier.authorityHo, JCM=rp00258-
dc.identifier.doi10.1200/JCO.2016.34.15_suppl.9060-
dc.identifier.hkuros273496-
dc.identifier.volume34-
dc.identifier.issue15, Suppl.-
dc.identifier.spageAbstract # 9060-
dc.identifier.epageAbstract # 9060-
dc.publisher.placeUnited States-

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