SHR-A1921

P2, N=120, Recruiting, Fudan University

P2, N=620, Recruiting, Fudan University | N=140 --> 620

P1/2, N=220, Active, not recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Recruiting --> Active, not recruiting | N=120 --> 220

P2, N=165, Recruiting, Shanghai Chest Hospital; Shanghai Chest Hospital

P1/2, N=70, Enrolling by invitation, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Enrolling by invitation

P3, N=440, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=716, Recruiting, Fudan University | Phase classification: P1/2 --> P2

P2, N=32, Not yet recruiting, shanghai pulmonary hospital; shanghai pulmonary hospital

P2, N=32, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China

P1/2, N=156, Not yet recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd.

P1, N=9, Completed, Atridia Pty Ltd. | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Apr 2024 | Trial primary completion date: Oct 2023 --> Apr 2024

P2, N=32, Not yet recruiting, Fudan University

P2, N=30, Not yet recruiting, Henan Cancer Hospital

P2, N=131, Not yet recruiting, Beijing GoBroad Hospital

P1/2, N=124, Not yet recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd.

P3, N=440, Not yet recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd.

P1/2, N=70, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.

P2, N=88, Recruiting, Fudan University | N=66 --> 88

P2, N=24, Not yet recruiting, Fudan University

P2/3, N=520, Not yet recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd.

P1, N=9, Active, not recruiting, Atridia Pty Ltd. | Recruiting --> Active, not recruiting | N=35 --> 9

P2, N=30, Recruiting, Peking Union Medical College

P2, N=66, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=66, Not yet recruiting, Fudan University

P1/2, N=120, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting

SHR-A1921 showed a manageable safety profile and promising anti-tumor activity in patients with pretreated advanced cancer. The trial is ongoing to assess SHR-A1921 at different dosing frequency and the efficacy in selected cancer types.

Compared with other Trop-2-targeted ADCs in the field, such as Trodelvy, TINA-SHR79711 (a molecule synthesized using the published structure of DS-1062), and SKB264, SHR-A1921 has considerable advantages as follows: (1) Stronger binding affinity to both human and rhesus macaque TROP-2 than TINA-SHR79711; (2) Improved plasma stability in plasma of different species presumably due to the proper steric hindrance which was purposely designed on the payload for reducing non-intended cleavage; (3) Stronger bystander cell killing effect presumably due to the increased lipophilicity of the payload vs. that of the payload in TINA-SHR79711; (4) Superior in vivo efficacy in a PSCC2 CDX Model (FaDu) with high Trop-2 expression (TGI 101% vs 53% [TINA-SHR79711] @ 1 mpk) and in an ovarian cancer CDX Model (SK-OV-3) with moderate Trop-2 expression (TGI 63% vs. 23% [TINA-SHR79711] @ 3 mpk; 87% vs. 16% [TINA-SHR79711] @ 10 mpk); (5) ≥ 2X longer half-life in patients# vs. SKB264 vs. IMMU-132, supporting more flexible dosing frequency; (6) Lower free toxin/ADC ratio# regarding PK exposure in patients compared with SKB264 (< 1% vs. 5-6%); (7) approximately linear pharmacokinetics profile in patients with T1/2 ranging from 2.5 to 4.5 days. #. non-head-to-head comparison.)