Transcenta Holding Limited (HKG:6628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, announced that interim safety and efficacy data of dose expansion cohort from the phase I/II study of TST001 (Osemitamab), a humanized ADCC-enhanced anti-Claudin18.2 monoclonal antibody, in combination with Capecitabine and Oxaliplatin (CAPOX) as a first line treatment of locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer was presented in a poster at the European Society for Medical Oncology (ESMO) Congress 2022.
In first line treatment of advanced or metastatic G/GEJ cancer, early interim data of the first 15 patients with measurable disease receiving the combination of TST001 with CAPOX demonstrated a partial response rate of 73.3% and a disease control rate of 100% per RECIST1.1. Based on these encouraging data, the TST001 program is further accelerated and Health Authority consultations are being initiated. A global phase III clinical program of TST001 (Osemitamab) for the first line treatment of locally advanced or metastatic Claudin18.2 positive G/GEJ cancer is currently being planned.
1. Claudin18.2 is expected to be the most shining star target in gastric cancer
The European Society for Medical Oncology (ESMO) Congress 2022 was held in person in Paris and virtually between 9-13 September 2022. Around 2000 abstracts and late-breaking abstracts were presented during the congress days. Transcenta’s poster with the dose expansion cohort interim data from the TST001 in combination with chemotherapy in first line treatment of locally advanced or metastatic G/GEJ cancer patients with Claudin18.2 expression was presented on Sept 12, 2022.
Data shows that as of August 4, 2022, 51 patients were enrolled and dosed including 36 patients treated with TST001 plus CAPOX at 6mg/kg Q3W in the expansion phase. Among the 15 patients with measurable disease and at least one post-treatment tumor assessment, 11 (73.3%) achieved partial response and four (26.7%) achieved stable disease. All 51 enrolled patients were evaluated for safety and tolerability. Treatment-emergent adverse events regardless of causality were mostly grade 1-2. Twelve (23.5%) patients experienced dose delay, five (9.8%) experienced dose reduction and no patient experienced discontinuation due to treatment related adverse events. In this study, TST001 also demonstrated a clear dose proportional pharmacokinetic profile, is consistent with those observed with TST001 monotherapy and in US patients. These data suggest that TST001 combined CAPOX is well tolerated and with promising efficacy in a broad gastric cancer patient population with tumors expressing Claudin18.2, including medium and high expressors. Furthermore, Transcenta has also developed a proprietary IHC assay to select patients with Claudin18.2 expressing tumors for registration enabling studies.
Despite progresses in the treatment of advanced gastric cancer with HER2, VEGF, VEGFR, or PD-1/PD-L1 targeted therapies, outcomes remain poor for 1st line patients with median overall survival of around 14 months. Claudin18.2 expression is observed at various levels in 50%-70% of gastric cancer patients, and at relatively high percentage in a variety of tumors including pancreatic, cholangiocarcinoma, ovarian and lung cancer. It is one of the hottest targets in cancer treatment. A few Claudin18.2 directed targeted drugs have entered the clinical stage, including monoclonal antibodies, bispecific antibodies, CAR-T and antibody-drug couples (ADCs). TST001, a humanized anti-Claudin18.2 monoclonal antibody, with higher target binding affinity and enhanced ADCC activity than other antibodies, has demonstrated very encouraging preliminary signs of activity in 1st L gastric / GEJ cancers with various levels of CLDN18.2 expression, and a manageable safety and tolerability profile.
Since entering into the clinical stage, Transcenta has attracted the attention of many multinational corporations. It established a global clinical collaboration with Bristol-Myers Squibb to evaluate the combination of TST001 with Opdivo(R) (Bristol-Myers Squibb’s anti-PD-1 therapy) for the treatment of patients with unresectable locally advanced or metastatic G/GEJ cancer earlier in March this year. These TST001 data have also generated a lot of excitement from GI cancers investigators who see TST001 as an effective new treatment option to cover the high unmet need of Claudin18.2 medium and high expressors cancers, providing a broader treatment option than other players in the same class. As TST001 data continue to mature, Transcenta progresses TST001 towards phase III trial and has initiated Health authority consultations.
2. Dr. Caroline Germa, former AstraZeneca Oncology’s Vice President, is now Transcenta’s Chief Medical Officer as the Company accelerates its expansion internationally
In August 2022, Transcenta announced the appointment of Dr. Caroline Germa as the Executive Vice President, Global Medicine Development and Chief Medical Officer. Dr. Caroline Germa was formerly Vice President of AstraZeneca Oncology and has extensive oncology development experience. Prior to joining AstraZeneca, she also worked for a number of world-renowned companies including Pfizer and Bristol-Myers Squibb, and led the late-stage clinical development of a number of key oncology assets, in particular the global registration strategy and approval of blockbuster drugs including Ribociclib (CDK4/6 inhibitor – Kisqali) and Neratinib. She has a deep understanding of the industry and, with her pharmaceutical industry contacts and unique ideas on the business development of the Company, international clinical development and regulatory approvals, the Company is confident that Dr Caroline Germa will be able to lead Transcenta to better global expansion and make a significant contribution to enhancing the Company’s shareholder value.
3. TST001 is ranked among the top two most advanced clinical programs for Claudin18.2 worldwide, and the first in China
Zolbetuximab is the first clinical stage anti-claudin18.2 monoclonal antibody. In a phase II, randomized study evaluating Zolbetuximab + epirubicin + oxaliplatin + capecitabine (EOX) for the first-line treatment of CLDN18.2 positive advanced G/GEJ cancer or esophageal adenocarcinoma, zolbetuximab plus EOX chemotherapy showed significant improvements in progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone in the overall population, padding the Claudin18.2 target’s potential for druggability. TST001 of Transcenta is a second generation anti-Claudin18.2 antibody with a differentiated profile relative to Zolbetuximab. It not only has 10-folds higher affinity binding to Claudin18.2, but also has a reduced fucose profile in the Fc of the humanized antibody. Combining these features, the ADCC activity of TST001 is 30-100 folds higher compared to Zolbetuximab analogue in tumor cells expressing various levels of Claudin18.2, which translated into much more potent in vivo anti-tumor activity, in particular, for those tumors expressing medium or low levels Claudin18.2.
TST001 is being developed in parallel in China and the US and is currently in Phase II clinical studies. It is expected to start the global pivotal trial for TST001 during the Mid-2023. In the meantime, Transcenta will continue to evaluate other combination therapies as well as other indications. As the Company continues to accelerate its clinical development and commercialization, Transcenta will eventually better realize more of its potential with its outstanding platform, increase the shareholder value and develop innovative drugs that will benefit patients worldwide.