Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors (GIST) As ≥4th Line Therapy: Long-term Update from a Single-Arm, Phase 2 Trial.

11543 Background: In INVICTUS study (NCT03353753), ripretinib as ≥4th line (4L) GIST therapy significantly improved median progression-free survival (mPFS) versus placebo (hazard ratio 0.15, 95% confidence interval [CI] 0.09–0.25; mPFS 6.3 vs 1.0 months) with a satisfactory safety profile. In the primary analysis (data cut-off: 26 Feb 2021) of the bridging study (NCT04282980) of INVICTUS, ripretinib as ≥4L therapy showed consistent efficacy and safety profiles in Chinese GIST patients to those in INVICTUS, with mPFS of 7.2 months and objective response rate (ORR) of 18.4% (7/38 patients). The overall survival (OS) data was immature at the primary analysis. Here we report the long-term updates of this bridging study. Methods: Patients received ripretinib 150 mg once daily continuously in 28-day cycles until progressive disease or other protocol-specified events for treatment discontinuation. The primary endpoint was progression-free survival (PFS) by independent radiologic review (IRR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 GIST-Specific Standard. Secondary endpoints included ORR by IRR, time to best response (TBR), duration of response (DOR), OS and safety. Adverse events were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. Results: Overall, 39 patients were enrolled. Thirty-eight patients received continuous ripretinib treatment and were included in the efficacy analysis set. All 39 patients received at least one dose of ripretinib and were included in the safety set. The updated data cut-off was 23 Aug 2022. The overall median follow-up (90% CI) was 23.00 (11.99, 24.87) months. In the efficacy analysis set, mPFS (90% CI) by IRR was 6.44 (2.89, 8.31) months and ORR was 21.1% (8/38 patients). Median TBR and median DOR for the 8 patients with confirmed partial response were 2.25 and 8.57 months, respectively. The median OS (95% CI) in the efficacy analysis set was 25.56 (11.73, not evaluable) months. In the safety set, 20.5% of patients experienced ≥1 grade 3/4 treatment-related treatment-emergent adverse events (TRAEs). Compared to the primary analysis, the increase in TRAEs and new TRAEs leading to dose modification were minimal after 18 months of additional follow-up. Conclusions: After long-term follow-up, the more mature results continued to support the clinically meaningful benefit in PFS and also demonstrated clinically meaningful benefit in OS in Chinese ≥4L GIST patients, while the safety profile remained satisfactory. Clinical trial information: NCT04282980 .