2023 - 10 - 23
Latest data reveals a 55% confirmed response rate, median duration of response (DoR) and median progression-free survival (PFS) of more than 12 months for all patients treated in the expansion cohort
Princeton, New Jersey & SUZHOU, China, October 23, 2023 -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical-stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, announces that it has presented updated efficacy data from the expansion cohort of the TranStar102 of Osemitamab (TST001) plus CAPOX chemotherapy study as the first-line treatment of advanced G/GEJ Cancer at the ESMO Congress 2023 in Madrid, Spain. The updated data continued to show encouraging efficacy from previously disclosed data in patients with CLDN18.2 expression ≥10%, ≥1+ per the LDT assay used to select patients. Two additional posters were presented: one on preclinical data supporting the triple combination of Osemitamab (TST001), nivolumab and chemotherapy over Osemitamab (TST001) and chemotherapy including in PD-L1 negative tumors; and one detailing the clinical pharmacology explorations supporting the recommended Phase III dose.
“These latest datasets further solidify the evidence affirming the efficacy that Osemitamab (TST001) plus CAPOX chemotherapy can provide as a first-line treatment for advanced gastric and gastroesophageal cancer including in tumors with lower levels of CLDN18.2 expression, and provide the rationale to explore the triple combination of Osemitamab (TST001), nivolumab and chemotherapy regardless of the PD-L1 CPS levels.” said Dr. Caroline Germa, Transcenta’s Executive Vice President, Global Medicine Development and Chief Medical Officer. “We are highly encouraged by the compelling efficacy outcomes from this study in addition to the recent FDA approval to initiate a global Phase III clinical trial, which signifies that Osemitamab (TST001) is poised to redefine the prevailing standard of care for patients with CLDN18.2 positive, HER2 negative gastric and gastroesophageal cancers.”
Cohort C from Transtar102 study (NCT04495296) was designed to explore the safety and efficacy of Osemitamab (TST001) plus CAPOX as first-line treatment in advanced G/GEJ cancer. In this study, 49 patients were enrolled and treated with 6mg/kg Q3W Osemitamab (TST001) and CAPOX in the efficacy expansion cohort.
Among the 49 patients enrolled, 41 patients had CLDN18.2 positive tumors, and the other 8 patients did not have the biomarker tested. CLDN18.2 expression were tested using the IHC 14G11 LDT assay in a central laboratory. CLDN18.2 positive tumor was defined as ≥ 10% tumor cells staining at least 1+ by the LDT assay, which represents approximately 55% of all the G/GEJ cancer patients.
Encouraging and Durable mDOR and mPFS
At the cut-off date reported here, the median follow-up for the 49 patients was 11.3 months with the longest treatment duration over 1.5 years. Among the 49 patients, 42 patients had measurable lesions at baseline and at least one post-baseline tumor assessment, and 28 of them achieved partial response, with 23 as confirmed response (54.8%, 23/42). The median duration of response (DoR) of these 23 responders was 12.7 months. 20 patients of the 49 patients had progression of disease or death, with an estimated median progression-free survival (PFS) of 14 months. The median overall survival (OS) was not reached because of the limited number of events, the 12-month survival rate for the overall population of cohort-C (64 patients, all doses) was 88.9% (95% CI: 74.2, 95.4). This further supports the Phase III trial strategy of combining Osemitamab (TST001) with nivolumab and chemotherapy in 1L CLDN18.2 positive G/GEJ cancer which Transcenta received FDA clearance recently.
Favorable and Manageable Safety Profile
The safety profile of these 49 patients was mainly characterized by manageable on-target-off-tumor effects, including nausea, hypoalbuminemia, and vomiting, most of them were grade 1 or 2 and occurred during the first 2 cycles.
In addition, preclinical data presented at the congress (#1560P) showed significant upregulation of PD-L1 in gastric cancer cells and increased TIL infiltration into tumor upon treatment with Osemitamab (TST001). The combination of anti-CLDN18.2 Osemitamab (TST001) with PD1 inhibitor nivolumab and chemotherapy resulted in significant synergy including in a CLDN18.2 positive/PD-L1 negative PDX model of gastric cancer. 5/8, 2/8, 0/8, 0/8 of the mice treated with Osemitamab (TST001) plus nivolumab and chemotherapy, Osemitamab (TST001) and chemotherapy, nivolumab and chemotherapy or chemotherapy only achieved tumor clearance in the mouse model respectively.
In an ER analysis of data from 58 patients with 1L G/GEJ adenocarcinoma treated with Osemitamab (TST001) and CAPOX(#1556P), trends of longer PFS/DoR and higher durable ORR were associated with higher Osemitamab (TST001) exposure and was aligned with exposure range achieved by 6 mg/kg Q3W. Safety ER analyses didn’t demonstrate clinically significant increase in risk when dose increased from 3 to 6 mg/kg Q3W. Preliminary efficacy, safety and PK/PD data demonstrates favorable benefit risk profile and support future exploration of Osemitamab (TST001) at the dose of 6mg/kg Q3W or 4mg/kg Q2W.
About Osemitamab (TST001)
Osemitamab (TST001) is a high affinity humanized anti-CLDN18.2 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity ("ADCC"). It has shown potent anti-tumor activities in tumor xenograft models. Osemitamab (TST001) is the second most advanced CLDN18.2 targeting antibody being developed globally. Osemitamab (TST001) was generated using Transcenta's Immune Tolerance Breaking Technology (IMTB) platform. Osemitamab (TST001) kills CLDN18.2 expressing tumor cells by mechanisms of ADCC. Leveraging advanced bioprocessing technology, the fucose content of Osemitamab (TST001) was significantly reduced during the production, which further enhanced NK cells mediated ADCC activity of Osemitamab (TST001). Clinical trials for Osemitamab (TST001) are ongoing in the U.S. and China (NCT05190575, NCT04396821, NCT04495296, NCT05608785 / CTR20201281). Osemitamab (TST001) was granted Orphan Drug Designation in the U.S. by FDA for the treatment of patients with gastric or gastroesophageal junction (G/GEJ) and pancreatic cancer.
Transcenta Announces the Publication of Preclinical Results of [177Lu]Lu-TST001 Radionuclide Antibody Conjugate as Potential Novel Treatment Option for Metastatic Gastric Cancer in the European Journal of Nuclear Medicine and Molecular Imaging
Transcenta Unveils Updated Efficacy Data from Osemitamab (TST001) Plus CAPOX as First-Line Treatment for G/GEJ Cancer Study at ESMO 2023
FDA Grants Transcenta Clearance to Proceed with Global Phase III Trial of Osemitamab (TST001) as First-Line Treatment for Gastric/Gastroesophageal Cancer Patients
Transcenta Anti-sclerostin Monoclonal Antibody TST002 (Blosozumab) Received Approval from China CDE to Initiate Phase II Clinical Trial in Patients with Reduced Bone Mineral Density
Transcenta Received Approvals from China CDE and South Korea MFDS to Initiate TranStar 301 Global Phase III Pivotal Trial of Osemitamab (TST001)
Transcenta Presented PFS Data by CLDN18.2 Expression Level from Phase I/II Study of Osemitamab (TST001) plus CAPOX as the First-Line Treatment of Advanced G/GEJ Cancer at 2023 ESMO GI Annual Congress