--- title: Professor Jin Li's Team Reports Phase I Results of Trastuzumab Rezetecan in HER2-Expressing Gastric/GEJ Adenocarcinoma and Colorectal Cancer url: "https://www.yyhmedical.com/en/news/ruikang-trastuzumab-her2-gastric-colorectal-phase1" type: Article inLanguage: en-US category: Medical Advances datePublished: 2026-03-11 --- # Professor Jin Li's Team Reports Phase I Results of Trastuzumab Rezetecan in HER2-Expressing Gastric/GEJ Adenocarcinoma and Colorectal Cancer > Phase I data for trastuzumab rezetecan, a China-developed HER2-targeted antibody-drug conjugate (ADC), in gastric and colorectal cancer have been published in the Journal of Clinical Oncology (JCO), showing encouraging antitumor activity with a manageable safety profile. Summary: Professor Jin Li's team at Shanghai GoBroad Cancer Hospital, Affiliated to China Pharmaceutical University, published Phase I clinical data in the Journal of Clinical Oncology on trastuzumab rezetecan, a China-developed HER2-targeted antibody-drug conjugate, in patients with advanced gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma and colorectal cancer (CRC). The study enrolled 100 patients. Among patients with HER2-positive GC/GEJ, the objective response rate (ORR) was 45.0% and median progression-free survival (PFS) was 9.0 months. Among patients with HER2-positive CRC, the ORR was 40.5% and median PFS was 9.5 months. The Phase I results showed promising preliminary efficacy and a manageable safety profile. On March 4, Phase I clinical data were published for trastuzumab rezetecan, a novel HER2-targeted antibody-drug conjugate (ADC) developed in China, in patients with advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJ) and colorectal cancer (CRC). The results appeared in the Journal of Clinical Oncology (JCO; impact factor 43.4), a leading journal in oncology. Professor Jin Li of Shanghai GoBroad Cancer Hospital, Affiliated to China Pharmaceutical University, served as the corresponding author. The preliminary findings showed encouraging antitumor activity and a manageable safety profile in patients with HER2-expressing GC/GEJ and CRC.\[1\] ![c02acb57-a9c6-4d05-b5e0-10e473618544.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/0f78385cf31a0445e6f70c7e85ea1ae6_20260914012131.png "0f78385cf31a0445e6f70c7e85ea1ae6_20260914012131.png") Study Published in JCO **Background** According to GLOBOCAN 2022, GC/GEJ ranks fifth globally for both incidence and mortality, while CRC ranks third for incidence and second for mortality, making both major global health burdens.\[2\] HER2 alterations are associated with the development and progression of multiple cancers and have become an important therapeutic target in several tumor types, including gastrointestinal cancers.\[3,4\] HER2 is expressed in approximately 40% of patients with GC/GEJ\[5\] and is overexpressed in about 3%-11% of patients with CRC. Trastuzumab rezetecan (development code SHR-A1811) is a next-generation HER2-targeted ADC. It consists of trastuzumab linked through a cleavable linker to SHR169265, a potent DNA topoisomerase I inhibitor. Its design combines a highly active payload with a relatively low drug-to-antibody ratio (DAR), with the aim of balancing antitumor activity and safety. ![7dbae056-405f-4326-bc00-5dbb202c8a32.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/3fc828160954d8f8d5459a12d647f35f_20260914012149.png "3fc828160954d8f8d5459a12d647f35f_20260914012149.png") Figure 1. Structure of Trastuzumab Rezetecan **Study Design and Methods** This Phase I trial included three parts: dose escalation, pharmacokinetic expansion, and clinical expansion. Eligible patients had HER2-expressing GC/GEJ or CRC (IHC 1+, 2+, or 3+, or ISH-positive) and had either failed standard treatment, were unable to tolerate standard treatment, or had no available standard treatment option. Dose escalation used the i3+3 design, with trastuzumab rezetecan administered at 3.2 mg/kg, 4.8 mg/kg, 6.4 mg/kg, and 8.0 mg/kg. Two to three dose levels were selected for pharmacokinetic expansion, followed by further collection of safety and efficacy data in the clinical expansion phase. ![c0fd20c6-3d92-4cb1-978f-b39ed4b4e3d8.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/fcb8e88d0a003759339a59691ec7dcfe_20260914012203.png "fcb8e88d0a003759339a59691ec7dcfe_20260914012203.png") Figure 2. Study Design **Study Results** **1\. Baseline Patient Characteristics** A total of 100 patients were enrolled: 15 in dose escalation, 18 in pharmacokinetic expansion, and 67 in clinical expansion. Fifty-seven patients had GC/GEJ (52 gastric cancer and 5 gastroesophageal junction cancer); 96.5% had an ECOG performance status of 1, and 50.9% had previously received anti-HER2 therapy. Forty-three patients had CRC (11 left-sided colon, 12 right-sided colon, and 20 rectal cancers); 90.7% had an ECOG performance status of 1, and 27.9% had previously received anti-HER2 therapy. As of February 29, 2024, 11 patients remained on treatment and 89 had discontinued, mainly because of disease progression. ![1418162c-4f6c-4516-951a-326293accd07.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/5479b787e5cad688fd6204942d70ec1c_20260914012228.png "5479b787e5cad688fd6204942d70ec1c_20260914012228.png") Table 1. Baseline Patient Characteristics **2\. Clinical Efficacy** All 100 patients received at least one dose of trastuzumab rezetecan, including 57 patients with HER2-expressing GC/GEJ and 43 with HER2-expressing CRC. As of February 29, 2024, the median follow-up was 11.4 months for the GC/GEJ group and 13.8 months for the CRC group. Among 40 patients with HER2-positive GC/GEJ, the ORR was 45.0%, the disease control rate (DCR) was 87.5%, median duration of response (DoR) was 5.5 months, median PFS was 9.0 months, and median overall survival (OS) was 16.3 months. Among 28 patients who had previously received HER2-targeted therapy, 14 achieved a response, for an ORR of 50.0%. In 12 patients with HER2 IHC 2+/ISH-negative GC/GEJ, the ORR was 25.0%, DCR was 91.7%, median PFS was 12.2 months, and median OS was not yet mature. Among 32 patients with GC/GEJ who received trastuzumab rezetecan at 6.4 mg/kg, the ORR was 50.0%, DCR was 84.4%, median DoR was 5.7 months, median PFS was 8.4 months, and median OS was 16.3 months. Among 37 patients with HER2-positive CRC, the ORR was 40.5%, DCR was 91.9%, median DoR was 6.1 months, median PFS was 9.5 months, and median OS was 22.7 months. Among 11 patients who had previously received HER2-targeted therapy, 4 achieved a response, for an ORR of 36.4%. Among 32 patients with HER2-positive CRC who received trastuzumab rezetecan at 6.4 mg/kg, the ORR was 40.6% and DCR was 93.8%; median PFS was 9.5 months and median OS was 22.7 months. ![e68cbe77-d6b3-403f-8fe2-c646655758cc.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/7a20a82a4ad9b1c38b9fb62f83bb7321_20260914012243.png "7a20a82a4ad9b1c38b9fb62f83bb7321_20260914012243.png")  Table 2. Tumor Response ![b19bb0b5-a06e-46ff-bb28-e0657562e346.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/ec9531ea721752a13f14216bdd51acad_20260914012253.png "ec9531ea721752a13f14216bdd51acad_20260914012253.png") Figure 3. Waterfall Plot: Best Percentage Change from Baseline in Target Lesions in Patients with HER2-Positive or HER2 IHC 2+/ISH-Negative GC/GEJ ![02bfe7b2-aee0-4516-a6bc-c2a68cbf76b4.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/7f1ceaadc48ec5d8f4f793c84858644b_20260914012306.png "7f1ceaadc48ec5d8f4f793c84858644b_20260914012306.png")  Figure 4. Swimmer Plot: Tumor Response in Patients with HER2-Positive GC/GEJ ![40b7ec00-4f34-4584-80bd-5ee4f9a8ef5a.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/4b4f64618d891837663b7db8270a55fa_20260914012317.png "4b4f64618d891837663b7db8270a55fa_20260914012317.png") Figure 5. Swimmer Plot: Tumor Response in Patients with HER2 IHC 2+/ISH-Negative GC/GEJ ![2e0d4eb1-8a6f-4244-a69e-d9b9adafa386.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/42c5bc656c8a18055149cfe1c71e2e9c_20260914012330.png "42c5bc656c8a18055149cfe1c71e2e9c_20260914012330.png") Figure 6. Waterfall Plot: Best Percentage Change from Baseline in Target Lesions in Patients with HER2-Positive CRC ![cbce1b32-3d8a-423d-bc18-ece1742a64b4.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260914/0f4addf2238e34dd43082c6cd30bc954_20260914012342.png "0f4addf2238e34dd43082c6cd30bc954_20260914012342.png") Figure 7. Swimmer Plot: Tumor Response in Patients with HER2-Positive CRC **3\. Safety** Of the 100 patients, 96 (96%) experienced treatment-related adverse events (TRAEs) of any grade, and 66 (66%) reported grade 3 or 4 TRAEs. The most common included decreased neutrophil count (49 patients, 49%), decreased white blood cell count (39 patients, 39%), and anemia (29 patients, 29%). Serious TRAEs occurred in 33 patients (33.0%), including decreased platelet count in 10 patients (10.0%), anemia in 8 (8.0%), and decreased neutrophil count in 7 (7.0%). **Summary** Overall, trastuzumab rezetecan showed encouraging antitumor activity with a manageable safety profile in patients with advanced GC/GEJ and CRC. A Phase III study of trastuzumab rezetecan as second-line treatment for GC/GEJ (NCT06123494) is ongoing. In addition, the marketing application for a new colorectal cancer indication has been accepted by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration and granted priority review. These developments may bring additional treatment options to patients in the future. References: \[1\] Liu T, Luo S, Yuan X, et al. Trastuzumab Rezetecan in Human Epidermal Growth Factor Receptor 2-Expressing Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma and Colorectal Cancer: A Multicenter, Open-Label, Phase I Trial. J Clin Oncol. Published online March 4, 2026. \[2\] Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. \[3\] Zhu K, Yang X, Tai H, Zhong X, Luo T, Zheng H. HER2-targeted therapies in cancer: a systematic review. Biomark Res. 2024;12(1):16 \[4\] Ingold Heppner B, Behrens HM, Balschun K, et al: HER2/neu testing in primary colorectal carcinoma. Br J Cancer 111:1977-84, 2014 \[5\]  Van Cutsem E, Bang YJ, Feng-Yi F, et al: HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 18:476-84, 2015 --- Original (HTML):https://www.yyhmedical.com/en/news/ruikang-trastuzumab-her2-gastric-colorectal-phase1 This is a clean Markdown mirror for large language models; the original page is authoritative.