Phase 1 study of HRS-6209, a highly selective CDK4 inhibitor, in patients with advanced solid tumors
Presenter: Lin Dong Session: Phase 0 and First-in-Human Phase I Clinical Trials Time: 4/20/2026 2:00:00 PM → 4/20/2026 5:00:00 PM
Authors
Jiong Wu 1 , Jian Zhang 1 , Ning Lu 2 , Caigang Liu 3 , Qiang Ding 4 , Huangming Hong 5 , Hui Wang 6 , Yuping Sun 7 , Hong Zhang 8 , Min Yan 9 , Ying Wang 10 , Yiqun Du 1 , Yanchun Meng 1 , Dongfang Li 6 , Huihui Li 7 , Zhengkui Sun 8 , Xiaoyu Zhu 11 , Xia Zhang 11 , Xiaonan Sheng 11 , Qiushi Xie 11 , Mengzhu Yu 11 1 Fudan University Shanghai Cancer Center, Shanghai, China, 2 Tianjin Medical University Cancer Institute & Hospital, Tianjin, China, 3 Shengjing Hospital of China Medical University, Shenyang, China, 4 Jiangsu Provincial People’s Hospital (The First Affiliated Hospital of Nanjing Medical University), Nanjing, China, 5 Sichuan Cancer Hospital, Chengdu, China, 6 Hunan Cancer Hospital, Changsha, China, 7 Affiliated Cancer Hospital of Shandong First Medical University, Jinan, China, 8 Jiangxi Provincial Cancer Hospital, Nanchang, China, 9 The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China, 10 Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China, 11 Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China
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 T max 2-4 h, mean t 1/2 8.94-9.96 h, and accumulation ratios of 1.27-1.61 for C max and 1.45-1.70 for AUC 0-12 . 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. Table 1. Key baseline characteristics and efficacy in patients with HR+/HER2- breast cancer 50 mg BID (n=15) 75 mg BID (n=16) 100 mg BID (n=13) All (n=48) Prior lines of endocrine therapy in metastatic setting (median) 2.0 1.0 2.0 1.5 Prior lines of chemotherapy in metastatic setting (median) 1.0 0 1.0 1.0 Confirmed ORR, % (n/N; 95% CI) 6.7 (1/15; 0.2-32.0) 6.3 (1/16; 0.2-30.2) 7.7 (1/13; 0.2-36.0) 6.3 (3/48; 1.3-17.2) Clinical benefit rate*, % (n/N; 95% CI) 26.7 (4/15; 7.8-55.1) 56.3 (9/16; 29.9-80.3) 53.8 (7/13; 25.1-80.8) 43.8 (21/48; 29.5-58.8) Median PFS, mo (95% CI) 1.8 (1.7, 4.2) 7.4 (1.9, NA) 9.1 (1.9, 14.5) 5.5 (3.7, 7.7) * Defined as complete or partial response, or stable disease lasting ≥24 weeks.
Disclosure
J. Wu, None.. J. Zhang, None.. N. Lu, None.. C. Liu, None.. Q. Ding, None.. H. Hong, None.. H. Wang, None.. Y. Sun, None.. H. Zhang, None.. M. Yan, None.. Y. Wang, None.. Y. Du, None.. Y. Meng, None.. D. Li, None.. H. Li, None.. Z. Sun, None. X. Zhu, Jiangsu Hengrui Pharmaceuticals Co., Ltd. Employment. X. Zhang, Jiangsu Hengrui Pharmaceuticals Co., Ltd. Employment. X. Sheng, Jiangsu Hengrui Pharmaceuticals Co., Ltd. Employment. Q. Xie, Jiangsu Hengrui Pharmaceuticals Co., Ltd. Employment. M. Yu, Jiangsu Hengrui Pharmaceuticals Co., Ltd. Employment.
Cited in
Control: 10088 · Presentation Id: 12042 · Meeting 21436