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.