Phase II trial of ponatinib in patients with metastatic gastrointestinal stromal tumor following failure or intolerance of prior therapy with imatinib (POETIG Trial): clinical cancer research : clinical trials : targeted therapy
Imatinib resistance is conferred by secondary mutations within the ATP-binding pocket or the activation loop of KIT in gastrointestinal stromal tumors (GIST). Ponatinib is active against KIT secondary activation loop and the gatekeeper mutation T670I in vitro. We evaluated the safety, activity, and...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
October 1, 2025
|
| In: |
Clinical cancer research
Year: 2025, Jahrgang: 31, Heft: 19, Pages: 4059-4069 |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-25-0222 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-25-0222
|
| Verfasserangaben: | Johanna Falkenhorst, Philipp Ivanyi, Tom Schulz, Rainer Hamacher, Bernd Kasper, Peter Hohenberger, Christoph K.W. Deinzer, Daniel Pink, Benjamin S. Fletcher, Valerie Haller, Yasmin Optaczy, Susanne Grunewald, Daniel Rauh, Adrian Mariño-Enríquez, Thomas Mühlenberg, Peter Reichardt, and Sebastian Bauer |
MARC
| LEADER | 00000naa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1946495999 | ||
| 003 | DE-627 | ||
| 005 | 20251218101749.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 251218s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1158/1078-0432.CCR-25-0222 |2 doi | |
| 035 | |a (DE-627)1946495999 | ||
| 035 | |a (DE-599)KXP1946495999 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Falkenhorst, Johanna |d 1989- |e VerfasserIn |0 (DE-588)1168241707 |0 (DE-627)1031898093 |0 (DE-576)511478054 |4 aut | |
| 245 | 1 | 0 | |a Phase II trial of ponatinib in patients with metastatic gastrointestinal stromal tumor following failure or intolerance of prior therapy with imatinib (POETIG Trial) |b clinical cancer research : clinical trials : targeted therapy |c Johanna Falkenhorst, Philipp Ivanyi, Tom Schulz, Rainer Hamacher, Bernd Kasper, Peter Hohenberger, Christoph K.W. Deinzer, Daniel Pink, Benjamin S. Fletcher, Valerie Haller, Yasmin Optaczy, Susanne Grunewald, Daniel Rauh, Adrian Mariño-Enríquez, Thomas Mühlenberg, Peter Reichardt, and Sebastian Bauer |
| 264 | 1 | |c October 1, 2025 | |
| 300 | |b Diagramme | ||
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 18.12.2025 | ||
| 520 | |a Imatinib resistance is conferred by secondary mutations within the ATP-binding pocket or the activation loop of KIT in gastrointestinal stromal tumors (GIST). Ponatinib is active against KIT secondary activation loop and the gatekeeper mutation T670I in vitro. We evaluated the safety, activity, and inhibitory profile of lower-dose (30 mg) ponatinib in pretreated patients with KIT-mutant GIST.POETIG was a multicenter phase II trial in patients with advanced, unresectable GIST progressing after imatinib (cohort A, KITV654A-, and cohort B, KITV654A+) or at least imatinib, sunitinib, and regorafenib (cohort C). The primary endpoint was the clinical benefit rate at 16 weeks (modified RECIST 1.1). ctDNA was analyzed for mutations V654A and T670I, and ponatinib was characterized in silico and in vitro using a panel of GIST cell lines.A total of 46 patients were enrolled, and the median follow-up was 1.3 years. The 16-week clinical benefit rate in cohorts A + B was five of 19 (26.3%) and nine of 27 (33.3%) in cohort C, with a median progression-free survival of 2.1 and 3.4 months with four (cohorts A + B) and five (cohort C) patients responding for >6 months. These patients were characterized by exon 11 and/or T670I mutations. Cardiovascular events occurred in four of 46 patients; most common grade 3/4 side effects were hypertension, gamma-glutamyl transferase (GGT)/lipase increase, abdominal pain, and infections. Clinical observations were reproduced by cell line screening and structural modeling.The trial did not meet its primary endpoint, but lower-dosed ponatinib provided clinical benefit in a subset of patients with expected toxicities. Patients harboring primary exon 11 and/or resistance mutations in T670I and/or exons 17/18 may represent a relevant therapeutic niche for ponatinib. | ||
| 700 | 1 | |a Ivanyi, Philipp |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schulz, Tom |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hamacher, Rainer |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kasper, Bernd |d 1974- |e VerfasserIn |0 (DE-588)12274764X |0 (DE-627)082130736 |0 (DE-576)29340447X |4 aut | |
| 700 | 1 | |a Hohenberger, Peter |d 1953- |e VerfasserIn |0 (DE-588)1025311469 |0 (DE-627)72202875X |0 (DE-576)370195574 |4 aut | |
| 700 | 1 | |a Deinzer, Christoph K.W. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pink, Daniel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fletcher, Benjamin S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Haller, Valerie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Optaczy, Yasmin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Grunewald, Susanne |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rauh, Daniel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mariño-Enríquez, Adrian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mühlenberg, Thomas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Reichardt, Peter |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bauer, Sebastian |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical cancer research |d Philadelphia, Pa. [u.a.] : AACR, 1995 |g 31(2025), 19, Seite 4059-4069 |h Online-Ressource |w (DE-627)325489971 |w (DE-600)2036787-9 |w (DE-576)094502234 |x 1557-3265 |7 nnas |a Phase II trial of ponatinib in patients with metastatic gastrointestinal stromal tumor following failure or intolerance of prior therapy with imatinib (POETIG Trial) clinical cancer research : clinical trials : targeted therapy |
| 773 | 1 | 8 | |g volume:31 |g year:2025 |g number:19 |g pages:4059-4069 |g extent:11 |a Phase II trial of ponatinib in patients with metastatic gastrointestinal stromal tumor following failure or intolerance of prior therapy with imatinib (POETIG Trial) clinical cancer research : clinical trials : targeted therapy |
| 856 | 4 | 0 | |u https://doi.org/10.1158/1078-0432.CCR-25-0222 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |7 1 |
| 951 | |a AR | ||
| 992 | |a 20251218 | ||
| 993 | |a Article | ||
| 994 | |a 2025 | ||
| 998 | |g 1025311469 |a Hohenberger, Peter |m 1025311469:Hohenberger, Peter |d 60000 |d 61800 |e 60000PH1025311469 |e 61800PH1025311469 |k 0/60000/ |k 1/60000/61800/ |p 6 | ||
| 998 | |g 12274764X |a Kasper, Bernd |m 12274764X:Kasper, Bernd |d 60000 |d 61200 |e 60000PK12274764X |e 61200PK12274764X |k 0/60000/ |k 1/60000/61200/ |p 5 | ||
| 999 | |a KXP-PPN1946495999 |e 4829867221 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"bibl":"article-journal","media":"Online-Ressource"},"note":["Gesehen am 18.12.2025"],"recId":"1946495999","language":["eng"],"person":[{"display":"Falkenhorst, Johanna","roleDisplay":"VerfasserIn","role":"aut","family":"Falkenhorst","given":"Johanna"},{"role":"aut","display":"Ivanyi, Philipp","roleDisplay":"VerfasserIn","given":"Philipp","family":"Ivanyi"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Schulz, Tom","given":"Tom","family":"Schulz"},{"roleDisplay":"VerfasserIn","display":"Hamacher, Rainer","role":"aut","family":"Hamacher","given":"Rainer"},{"given":"Bernd","family":"Kasper","role":"aut","roleDisplay":"VerfasserIn","display":"Kasper, Bernd"},{"roleDisplay":"VerfasserIn","display":"Hohenberger, Peter","role":"aut","family":"Hohenberger","given":"Peter"},{"display":"Deinzer, Christoph K.W.","roleDisplay":"VerfasserIn","role":"aut","family":"Deinzer","given":"Christoph K.W."},{"given":"Daniel","family":"Pink","role":"aut","roleDisplay":"VerfasserIn","display":"Pink, Daniel"},{"roleDisplay":"VerfasserIn","display":"Fletcher, Benjamin S.","role":"aut","family":"Fletcher","given":"Benjamin S."},{"given":"Valerie","family":"Haller","role":"aut","roleDisplay":"VerfasserIn","display":"Haller, Valerie"},{"given":"Yasmin","family":"Optaczy","role":"aut","display":"Optaczy, Yasmin","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","display":"Grunewald, Susanne","role":"aut","family":"Grunewald","given":"Susanne"},{"given":"Daniel","family":"Rauh","role":"aut","display":"Rauh, Daniel","roleDisplay":"VerfasserIn"},{"family":"Mariño-Enríquez","given":"Adrian","roleDisplay":"VerfasserIn","display":"Mariño-Enríquez, Adrian","role":"aut"},{"family":"Mühlenberg","given":"Thomas","roleDisplay":"VerfasserIn","display":"Mühlenberg, Thomas","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Reichardt, Peter","role":"aut","family":"Reichardt","given":"Peter"},{"given":"Sebastian","family":"Bauer","role":"aut","roleDisplay":"VerfasserIn","display":"Bauer, Sebastian"}],"title":[{"title_sort":"Phase II trial of ponatinib in patients with metastatic gastrointestinal stromal tumor following failure or intolerance of prior therapy with imatinib (POETIG Trial)","title":"Phase II trial of ponatinib in patients with metastatic gastrointestinal stromal tumor following failure or intolerance of prior therapy with imatinib (POETIG Trial)","subtitle":"clinical cancer research : clinical trials : targeted therapy"}],"physDesc":[{"noteIll":"Diagramme","extent":"11 S."}],"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"origin":[{"publisherPlace":"Philadelphia, Pa. [u.a.]","dateIssuedDisp":"1995-","dateIssuedKey":"1995","publisher":"AACR"}],"id":{"issn":["1557-3265"],"zdb":["2036787-9"],"eki":["325489971"]},"name":{"displayForm":["American Association for Cancer Research"]},"pubHistory":["1.1995 -"],"part":{"issue":"19","pages":"4059-4069","year":"2025","extent":"11","volume":"31","text":"31(2025), 19, Seite 4059-4069"},"type":{"media":"Online-Ressource","bibl":"periodical"},"disp":"Phase II trial of ponatinib in patients with metastatic gastrointestinal stromal tumor following failure or intolerance of prior therapy with imatinib (POETIG Trial) clinical cancer research : clinical trials : targeted therapyClinical cancer research","note":["Gesehen am 08.06.2023","Fortsetzung der Druck-Ausgabe"],"corporate":[{"role":"isb","display":"American Association for Cancer Research","roleDisplay":"Herausgebendes Organ"}],"language":["eng"],"recId":"325489971","title":[{"title":"Clinical cancer research","title_sort":"Clinical cancer research"}]}],"name":{"displayForm":["Johanna Falkenhorst, Philipp Ivanyi, Tom Schulz, Rainer Hamacher, Bernd Kasper, Peter Hohenberger, Christoph K.W. Deinzer, Daniel Pink, Benjamin S. Fletcher, Valerie Haller, Yasmin Optaczy, Susanne Grunewald, Daniel Rauh, Adrian Mariño-Enríquez, Thomas Mühlenberg, Peter Reichardt, and Sebastian Bauer"]},"origin":[{"dateIssuedKey":"2025","dateIssuedDisp":"October 1, 2025"}],"id":{"doi":["10.1158/1078-0432.CCR-25-0222"],"eki":["1946495999"]}} | ||
| SRT | |a FALKENHORSPHASEIITRI1202 | ||