Abstract CT117: Phase 1 study of HRS-6209, a highly selective CDK4 inhibitor, in patients with advanced solid tumors

Abstract Background: This first-in-human, open-label, multicenter, dose-escalation and dose-expansion phase 1 study evaluated the safety, pharmacokinetics (PK), and preliminary efficacy of HRS-6209, a highly selective CDK4 inhibitor, in patients (pts) with advanced solid tumors. Methods: Pts with advanced solid tumors who progressed on standard therapies or lacked available options were eligible and received HRS-6209 monotherapy at 5 dose cohorts (100 mg QD, 50 mg BID, 75 mg BID, 100 mg BID and 200 mg BID). The primary objectives were to assess the safety/tolerability of HRS-6209 and determine the recommended phase 2 dose. Results: As of November 15, 2025, 56 pts were enrolled, including 48 (85.7%) with HR+/HER2− breast cancer. In HR+/HER2− breast cancer pts, the median prior lines of endocrine therapy and chemotherapy in the metastatic setting were 1.5 and 1.0, respectively; 32 (66.7%), 39 (81.3%), and 29 (60.4%) had received prior CDK4/6 inhibitor, aromatase inhibitor, and fulvestrant, respectively. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. TRAEs occurred in 55 (98.2%) pts. Grade ≥3 TRAEs were reported in 22 pts (39.3%), with the most common being decreased neutrophil count (18 [32.1%]), decreased WBC count (8 [14.3%]), and anemia (3 [5.4%]). No pts discontinued treatment due to TRAEs, and there were no treatment-related deaths. In HR+/HER2− breast cancer, ORR was 6.3% (3/48; 1 pt each at 50, 75, and 100 mg BID); CBR was 26.7%, 56.3%, and 53.8%, and median PFS was 1.8, 7.4, and 9.1 months at 50, 75, and 100 mg BID, respectively (Table 1). PK exposure was approximately dose proportional across 50-200 mg BID, with median Tmax 2-4 h, mean t1/2 8.94-9.96 h, and accumulation ratios of 1.27-1.61 for Cmax and 1.45-1.70 for AUC0-12. Conclusions: HRS-6209 was well-tolerated, exhibiting favorable safety and PK profiles in patients with advanced solid tumors, and demonstrated promising anti-tumor activity in pretreated patients with HR+/HER2- breast cancer. Citation Format: Jiong Wu, Jian Zhang, Ning Lu, Caigang Liu, Qiang Ding, Huangming Hong, Hui Wang, Yuping Sun, Hong Zhang, Min Yan, Ying Wang, Yiqun Du, Yanchun Meng, Dongfang Li, Huihui Li, Zhengkui Sun, Xiaoyu Zhu, Xia Zhang, Xiaonan Sheng, Qiushi Xie, Mengzhu Yu. Phase 1 study of HRS-6209, a highly selective CDK4 inhibitor, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT117.