創勝集團 - 全整合型國際化生物制藥公司

創勝集團, 生物藥, 抗體, 藥物研發

創勝集團 - 全整合型國際化生物制藥公司

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學術論文及會議壁報

評估Osemitamab (TST001)單藥或與納武單抗/标準療法聯用治療局部晚期或轉移性實體瘤美國患者I/IIa期臨床試驗(TranStar101)的安全性、耐受性和藥代動力學數據

10 Apr, 2024

Authors:

1Yelena Janjigian, 2Anthony Tolcher, 3Rutika Mehta, 4Michael Cecchini, 5Brian Van Tine, 6Madappa Kundranda, 7Alese Olatunji, 8Manish R. Patel, 9Jordan Berlin, 10Caio Max Sao Pedro Rocha-Lima, 11Dulabh Monga, 12Ben George, 13Aaron Scott, 14Zhenzhong Xia, 15Mohamed Elsafy, 15Erikca Jones, 15Zhenling Yao, 14Chuan Qi, 15Caroline Germa, 16Nash Gabrail.

1Memorial Sloan Kettering, 2New York, NY, NEXT Oncology, San Antonio, TX, 3Moffitt Cancer Center, Tampa, FL, 4Yale Cancer Center, New Haven, CT, 5Washington University, St. Louis, MO, 6Banner MD Anderson Cancer Center, Phoenix, AZ, 7Emory University, Atlanta, GA, 8Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, 9Vanderbilt University Medical Center, Nashville, TN, 10Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, 11Allegheny Health Network Cancer Institute, Pittsburgh, PA, 12Medical College of Wisconsin, Milwaukee, WI, 13The University of Arizona Cancer Center, Tucson, AZ, 14Transcenta Therapeutics Inc, Suzhou, China, 15Transcenta Therapeutics Inc, Princeton, NJ, 16Gabrail Cancer Center, Canton, OH


Background:

Osemitamab (TST001) is a novel, recombinant humanized IgG1 mAb with improved CLDN18.2 binding affinity and enhanced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) and can result in more efficient killing of tumor cells expressing human CLDN18.2 across a broad range of levels including low to medium expression.

 Here we report safety data of osemitamab monotherapy or in combination of other anti-tumor treatments from TranStar101 study in US population.

Discussion and Conclusion:

The safety profile of osemitamab in US patients, as evidenced by the incidence of treatment-related adverse events (TRAEs), is consistent with the safety profile reported in Chinese patients from study TranStar 102. Most common TRAEs are on target off tumor toxicities, due to CLDN18.2 only being expressed in mature stomach mucosa in normal tissue. Nausea, vomiting, fatigue are the most common TRAEs. This is also consistent with the data from phase 3 trials of zolbetuximab, another anti-CLDN18.2 monoclonal antibody.

Safety of osemitamab is manageable on 4 mg/kg Q2W and 6 mg/kg Q3W dose schedules as monotherapy and in combination with nivolumab or nivolumab and platinum and fluoropyrimidine. Adding osemitamab to this regimen didn’t significantly increase the incidence of TRAE≥G3.

The population PK analysis revealed similar AUC but lower Cmax and higher Ctrough following 4mg/kg Q2W compared to 6mg/kg Q3W,. This information, along with data from TranStar102 including the efficacy, ER and PD results from Q3W provides a basis for the selection of 4 mg/kg as the Q2W dose.