Long-term outcomes in GIST Trial 13-162: Phase II study of imatinib in combination with binimetinib in untreated patients with advanced gastrointestinal stromal tumor (GIST).

Abstract

11527 Background: ETV1 and KIT are lineage-specific master transcriptional and signaling survival factors in GIST. Dual lineage targeting of ETV1 by binimetinib and KIT by imatinib are synergistic in suppressing GIST tumorigenesis and growth in preclinical models. We previously reported positive data in a single-arm phase II study that the combination of binimetinib plus imatinib is highly effective with expected and manageable treatment-associated toxicities, in patients (pts) with treatment-naïve advanced GIST, (ASCO 2020 and https://ascopubs.org/doi/pdfdirect/10.1200/JCO.21.02029). Here, we present 10-year follow-up results. Methods: This trial is a single-center, single-arm, phase II study. Adult patients with unresectable or metastatic treatment-naïve GISTs received imatinib (400mg daily) and binimetinib (30mg twice daily), 28-day cycles. The clinical efficacy was evaluated using serial imaging every 8-12 weeks, per RECIST1.1 criteria including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Correlatives included tumor genomics, transcriptomes, and imatinib trough levels. Results: At data cutoff of Nov 21, 2024, 29/42 evaluable pts with advanced GIST of all genotypes, including 3 KIT/PDGFRA -WT, had confirmed RECIST1.1 partial response (PR). Best ORR was 69.0% (95% CI, 52.9% to 82.4%). Median PFS (mPFS) was 36.7 months (95%CI, 24.2 to not estimable [NE]). Median OS (mOS) was 92.5 months (95%CI, 61.0 to NE), and the median DSS (mDSS) was 93.2 months (95%CI, 92.5 to NE). 23/42 pts had undergone surgery, with R0/R1 resection in 18 patients. 7 pts were considered exceptional responders, whose pathology revealed ≥90% significant pathological responses (SPR) and remained no evidence of disease (NED) after surgery ≥45 months. 3 pts who did not have SPR and remained NED ≥58 months. Transcriptome and genomic analysis, and imatinib trough level in the presence of binimetinib are forthcoming. Conclusions: The 10-year follow-up analysis of the binimetinib plus imatinib combination phase II study demonstrated robust and sustained clinical benefit in PFS, OS and DSS for patients with treatment-naïve advanced GIST. The combination strategy warrants further evaluation in direct comparison with imatinib in the frontline treatment of GIST. Clinical trial information: NCT01991379 .