Abstract CT132: A Phase I/IIa clinical trial (TranStar101) to evaluate the safety, tolerability and pharmacokinetics of OSEMITAMAB administered as monotherapy or in combination with nivolumab or standard of care in patients with locally advanced or metastatic solid tumors

Abstract Introduction: TST001/osemitamab 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 cytotoxicity of tumors expressing human CLDN18. 2 across a broad range of levels including low to medium expression. Methods: This is an open-label, multi-center phase I/IIa first in human (FIH) study of osemitamab administered as monotherapy or in combination with nivolumab or standard of care for patients with locally advanced or metastatic solid tumors. The study includes two parts: Part A (completed), a dose escalation of osemitamab as a monotherapy in solid tumors, osemitamab intravenous infusion at dose from 1mg/kg to 10mg/kg and once every two weeks (Q2W) or once every three weeks (Q3W) were evaluated; Part B (ongoing) includes expansion cohorts of osemitamab in combination with other therapies (cohort A and B). Cohort A includes combination of osemitamab, nivolumab, and mFOLFOX6 as the 1st line treatment for G/GEJ cancer. Cohort B includes osemitamab in combination with nivolumab in advanced pre-treated G/GEJ cancer. Results: As of Nov. 30, 2023, 68 patients have been treated: 38 patients were enrolled in the Part A dose escalation, 13 in Part B Cohort A, and 17 in Part B Cohort B. The population (N=68) consisted of 59% males, median age 62 years and 50% with G/GEJ cancer. Doses evaluated are 3 to 10mg/kg Q3W and 1 to 6 mg/kg Q2W in part A. One dose limiting toxicity of Grade 3 infusion related reaction was reported at the 1mg/kg dose Q2W. The MTD was not reached. The recommended phase 2 dose was determined as 6mg/kg Q3W or 4mg/kg Q2W based on the totality of available safety, efficacy, PK/PD data including information from another phase I/II study (TranStar102). The most common TRAEs (occurred in ≥ 20% subjects) were nausea (73. 5%), vomiting (48. 5%), fatigue (30. 9%). TRAE of Grade ≥ 3 across all tested doses (3-10 mg/kg) that occurred in ≥3% of patients included nausea, vomiting, hypoalbuminemia, hypertension, infusion related reaction, and lymphocyte count increased. Within the dose ranges studied, PK exposures increased as dose increased. The mean CLss value of osemitamab ranged from 9. 4 to 13. 7 mL/day/kg across different dose levels, without a clear dose relationship. Mild accumulation was observed following Q2W and Q3W dosing. Conclusion: Osemitamab as monotherapy or in combination with nivolumab or mFOLFOX plus nivolumab is well tolerated and safe with a PK profile consistent with other studies (TranStar 102 study -NCT04495296). TranStar 101 is currently ongoing. More information will be shared. Clinical trial information: NCT04396821. Study Sponsor: Suzhou Transcenta Therapeutics Co. , Ltd. Citation Format: Yelena Janjigian, Anthony Tolcher, Rutika Mehta, Michael Cecchini, Brian Van Tine, Madappa Kundranda, Alese Olatunji, Manish R. Patel, Jordan Berlin, Caio Max Sao Pedro Rocha-Lima, Dulabh Monga, Ben George, Aaron Scott, Zhenzhong Xia, Mohamed Elsafy, Erikca Jones, Zhenling Yao, Chuan Qi, Caroline Germa, Nash Gabrail. A Phase I/IIa clinical trial (TranStar101) to evaluate the safety, tolerability and pharmacokinetics of OSEMITAMAB administered as monotherapy or in combination with nivolumab or standard of care in patients with locally advanced or metastatic solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT132.