Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and paraganglioma.

• DOI: 10.1200/jco.2024.42.16_suppl.11502
• Publication Date: 2024-06-13T13:41:56Z
• Authors: Haibo Qiu; Zhi-wei Zhou; Ye Zhou; Jie Chen; Xiangbin Wan; Ning Li; Kaixiong Tao; Yong Li; Xin Wu; Zi Chen; Lihui Liu; Chen Yang; Lichuang Men; Hengbang Wang; Eric Liang; Cunlin Wang; Lixin Jiang; Dajun Yang; Yifan Zhai; Rui-Hua Xu
• Keywords: 03 medical and health sciences; 0302 clinical medicine

11502 Background: SDH-deficient GIST is a rare type of GIST, mainly observed in the stomach of children and adolescents or young adults < 30 years of age. No active targeted therapies have been identified in this subset of GIST. Olverembatinib, approved in China for treatment of patients with chronic myeloid leukemia, has shown promising clinical efficacy in SDH-deficient GIST. We report here updated efficacy data in SDH-deficient GIST and preliminary efficacy data in paraganglioma, which is an SDH-deficient–related tumor. Methods: The aim of this study was to evaluate the safety and efficacy (per RECIST v1.1) of olverembatinib in patients with TKI-resistant SDH-deficient GIST and other solid tumors. Olverembatinib was administered orally once every other day (QOD) in 28-day cycles. Results: As of December 27, 2023, 26 patients with SDH-deficient GIST (confirmed by IHC) had received ≥ 1 dose of olverembatinib (median [range] age, 30 [13-56] years), and 25 had received 1 to 4 TKIs (42.3% of patients, ≥ 3; Table 1). Olverembatinib was administered QOD in doses ranging from 30 to 50 mg (30 mg [n = 6]; 40 mg [n = 14]; 50 mg [n = 6]). The median (range) treatment duration was 15.6 (1.8-42.3) months. A total of 6 of 26patients experienced partial response (PR) as the best response. A further 18 patients had stable disease (SD) lasting > 4 cycles. The clinical benefit rate (CBR; complete response [CR] + PR + SD > 4 cycles) was hence 92.3% (24/26) and the longest treatment duration was 40 months. After a median follow-up of 17.0 (4.1-57.5) months, the median progression-free survival (PFS) was 25.7 months (12.1-not reached [NR]). Among the 6 patients with paraganglioma enrolled in this study, best responses were observed in 5, with SD lasting > 4 cycles (CBR, 83.3%), and the median PFS was 8.25 (1.87-NR) months. The adverse event profile was the same as previously reported (Qiu H et al, J Clin Oncol 41:11540), with no newly emergent safety issues observed. Conclusions: Olverembatinib was well tolerated. The CBR exceeded 90%, and the estimated median PFS was significantly prolonged, indicating potential benefit of this treatment and providing a benchmark for future studies in this rare subtype of GIST. Clinical trial registration: NCT03594422; internal study identifier: SJ-0003. Clinical trial information: NCT03594422 .[Table: see text]