The efficacy and safety of RC88 in patients with ovarian cancer, non-squamous-non-small-cell lung-carcinoma and cervical cancer: Results from a first-in-human phase 1/2 study.

person Yutao Liu National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China info_outline Yutao Liu, Guiling Li, Runxiang Yang, Yu Huang, Suxia Luo, Qi Dang, Qingshui Li, Dingzhi Huang, Yi Huang, Dihong Tang, Xiubao Ren, Youzhong Zhang, Yuguang Zhao, Baorui Liu, Jin Zhou, Yanjie Wang, Heping Liu, Beisong Liu, Jianmin Fang, Yuankai Shi

Authors person Yutao Liu National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China info_outline Yutao Liu, Guiling Li, Runxiang Yang, Yu Huang, Suxia Luo, Qi Dang, Qingshui Li, Dingzhi Huang, Yi Huang, Dihong Tang, Xiubao Ren, Youzhong Zhang, Yuguang Zhao, Baorui Liu, Jin Zhou, Yanjie Wang, Heping Liu, Beisong Liu, Jianmin Fang, Yuankai Shi Organizations National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Yunnan Cancer Hospital, Kunming, China, Chongqing University Cancer Hospital, Chongqing, China, Henan Cancer Hospital, Zhengzhou, China, Shandong Cancer Hospital, Jinan, Shandong, China, Shandong Cancer Hospital, Jinan, China, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, Hubei Cancer Hospital, Wuhan, China, Hunan Cancer Hospital, Changsha, China, Qilu Hospital of Shandong University, Jinan, China, First Hospital of Jilin University, Changchun, China, Nanjing Drum Tower Hospital, Nanjing, China, Sichuan Cancer Hospital, Chengdu, China, RemeGen Co., Ltd., Yantai, China, School of Life Science and Technology, Tonji Univesity, Shanghai, China Abstract Disclosures Research Funding RemeGen Co., Ltd., Beijing, China Background: RC88 is a first-in-class, antibody-drug conjugate (ADC) targeting mesothelin (MSLN) with the payload of Monomethyl auristatin E. MSLN, a glycosylphosphatidylinositol-anchored protein, is overexpressed in several solid tumors with limited expression in normal tissues. RC88-C001 is a single-arm, open-label, multi-center phase 1/2 study evaluating RC88 in patients (pts) with MSLN-expressing advanced solid tumor (NCT04175847). This abstract mainly reports the efficacy results from the dose expansion part (phase 2) of the study. Methods: Pts with MSLN-expressing advanced malignant solid tumors that have failed after standard therapies were enrolled in this study. MSLN was tested by IHC. For phase 2 study, the primary endpoint was ORR by investigator per RECIST v1.1 with secondary endpoints including DCR, PFS, and safety. Results: As of 19 December, 2023, 164 pts with advanced solid tumor were enrolled. Dose escalation phase was completed, and 2.0 mg/kg and 2.5 mg/kg Q3W were expanded in phase 2. In ovarian cancer cohort, 60 pts were enrolled and all with 2+ or 3+ MSLN expression. Forty-two (70%) were FIGO stage IV. Thirty-three (55%) had prior bevacizumab, and 29 (48.3%) had prior PARPi. The number of previous lines of systemic therapy were 2-7. Fifty-four (90%) pts were platinum-resistant. Among the 43 pts with at least one post-baseline tumor assessment, the ORR was 37.2% (16/43). In pts with prior 2-4 lines of therapies, the ORR was 45.5% (10/22) in 2.0 mg/kg and 33.3% (2/6) in 2.5mg/kg. In non-squamous-non-small-cell lung-carcinoma, 26 pts progressed on previous systemic therapy were enrolled and 23 (88.4%) had received ≥ 2 lines of prior therapies. Twenty-three pts had one post-baseline tumor assessment; the ORR was 21.7% (5/23). Among the 15 pts without driver gene mutations, 11 (73%) had received prior platinum-doublet chemotherapy and PD-(L)1 inhibitor. The ORR was 33.3% (5/15) with 1 CR. In cervical cancer, 18 pts progressed on previous systemic therapy were enrolled. In 17 pts with one post-baseline tumor assessment, 11 (64.7%) had received ≥ 2 lines of prior therapies; 12 (70.5%) had prior platinum-doublet chemotherapy and PD-(L)1 inhibitor. The ORR was 35.3% (6/17). TEAEs were reported in 161 pts (98.2%), with 40.2% ≥grade 3 TEAEs. Twenty-three pts (14%) had SAE related to RC88. The most frequent TRAEs were white blood cell count decreased (46.3%), neutrophil count decreased (42.1%), anemia (34.1%), nausea (32.3%), and aspartate aminotransferase increased (31.1%). The overall safety profile was better in 2.0mg/kg than 2.5mg/kg, therefore 2.0mg/kg was chosen as RP2D in further studies in China. Conclusions: RC88 demonstrated tolerable safety and encouraging preliminary efficacy in MSLN-expressing solid tumors, warranting further investigations. Clinical trial information: NCT04175847.

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