POETIG Trial - POnatinib After rEsisTance to Imatinib in GIST

Summary

This is a non-randomized, open-label, multicenter phase 2 study to evaluate the efficacy and safety of ponatinib in patients with metastatic and/or unresectable GIST after prior failure or intolerability of imatinib. Patients will be enrolled into 1 of 2 cohorts based on absence (Cohort A) or presence (Cohort B) of KIT exon 13 resistance mutations as measured by liquid biopsy. A third cohort (Cohort C) will include patients who have received all approved lines of TKI treatments (imatinib, sunitinib and regorafenib).

Timeline

Start

2017-03-22

Primary completion

2018-09-22

Completion

2020-09-22

Publications

• Background Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, O'Hare T, Hu S, Narasimhan NI, Rivera VM, Clackson T, Turner CD, Haluska FG, Druker BJ, Deininger MW, Talpaz M. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012 Nov 29;367(22):2075-88. doi: 10.1056/NEJMoa1205127.
• Background Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Muller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes T, Goldman JM, Shah NP, Kantarjian H; PACE Investigators. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013 Nov 7;369(19):1783-96. doi: 10.1056/NEJMoa1306494. Epub 2013 Nov 1.
• Background Garner AP, Gozgit JM, Anjum R, Vodala S, Schrock A, Zhou T, Serrano C, Eilers G, Zhu M, Ketzer J, Wardwell S, Ning Y, Song Y, Kohlmann A, Wang F, Clackson T, Heinrich MC, Fletcher JA, Bauer S, Rivera VM. Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients. Clin Cancer Res. 2014 Nov 15;20(22):5745-5755. doi: 10.1158/1078-0432.CCR-14-1397. Epub 2014 Sep 19.
• George S, von Mehren M, Fletcher JA, Sun J, Zhang S, Pritchard JR, Hodgson JG, Kerstein D, Rivera VM, Haluska FG, Heinrich MC. Phase II Study of Ponatinib in Advanced Gastrointestinal Stromal Tumors: Efficacy, Safety, and Impact of Liquid Biopsy and Other Biomarkers. Clin Cancer Res. 2022 Apr 1;28(7):1268-1276. doi: 10.1158/1078-0432.CCR-21-2037.

Drugs

Indications