Phase II Trial of Ponatinib in Patients with Metastatic Gastrointestinal Stromal Tumor following Failure or Intolerance of Prior Therapy with Imatinib (POETIG Trial)

Cancer research · Gastrointestinal stromal tumor

The purpose of this Phase 1/2 master protocol study is to evaluate if DCC-3009 is safe, tolerable and works effectively in the treatment of GIST.

Ponatinib was evaluated in pre-treated patients with KIT‑mutant gastrointestinal stromal tumour (GIST). In a multicentre phase II trial (POETIG), 46 patients with unresectable, advanced GIST presenting secondary KIT mutations (V654A and/or T670I) or progress after imatinib, sunitinib and regorafenib were treated with 30 mg ponatinib. The primary end‑point was the clinical benefit rate (CBR) at 16 weeks per modified RECIST 1.1. The CBR in cohorts A+B (GIST progress after imatinib only) was 26.3 % and in cohort C (progress after imatinib + sunitinib + regorafenib) it was 33.3 %. Median progression‑free survival (PFS) was 2.1 months (A+B) and 3.4 months (C). Overall PFS and overall survival (OS) data were not reported. Cardiovascular toxicity was observed, with hypertension, elevated γ‑glutamyl transferase/lipase and infections as the most common grade 3/4 adverse events. The trial did not meet the primary endpoint but suggests a clinical niche for ponatinib in patients with primary exon 11 and/or secondary T670I or exons 17/18 mutations.

This statement summarizes the trial’s aim to assess the safety, tolerability, and efficacy of a novel therapy for GIST within a master protocol design, indicating an innovative approach to evaluate multiple treatment modules in a single study.

Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.

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