Phase II results reveal median PFS of 12.6 months in patients with CLDN18.2 high or medium expression, including in patients with PD-L1 CPS<5.

PRINCETON, N.J. and SUZHOU, China, May 23, 2024 /PRNewswire/ -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a global clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, today announced the results from the Phase I/IIa Cohort-G data for Osemitamab (TST001) plus Nivolumab and CAPOX as the first-line treatment of patients with advanced G/GEJ cancer. The study, which enrolled patients regardless of their CLDN18.2 and PD-L1 CPS expression, indicated encouraging efficacy data for the triple combination, especially in patients with high or medium (H/M) CLDN18.2 expression, regardless of their PD-L1 CPS value.

The results showed that median progression-free survival (mPFS) reached 12.6 months in patients with H/M CLDN18.2 expression, any PD-L1 CPS, as well as in the 80% of patients with PD-L1 CPS<5. Using the group of patients with very low/no CLDN18.2 expression as surrogate control, the HR for the triple combination is 0.443 (95%CI, 0.205-0.958) in favor of the H/M expressors and in these patients, the confirmed overall response rate was 68%.

The majority (approximately 80%) of CLDN18.2 positive patients are PD-L1 CPS<5. Previous studies have found that the combination of Zolbetuximab+CAPOX in CLDN18.2 positive patients, regardless of the PD-L1 status, leads to an improvement in PFS from 6.80 to 8.21 months (HR = 0.687 (95% CI, 0.544-0.866) (Source: Shah, Manish A et al. Nature Medicine 2023 Aug 29 (8): 2133-2141). However, Nivolumab plus chemotherapy treatment in patients whose PD-L1 CPS is less than 5 produces very little benefit in PFS (median 7.5 vs 8.2 months with an HR of 0.93). (Source: Checkmate-649 study.) This Phase I/IIa Cohort-G data shows that the efficacy from the triple combo therapy of Osemitamab (TST001) plus Nivolumab and CAPOX compares very favorably with the historical data of Nivolumab plus CAPOX combination or Zolbetuximab plus CAPOX combination, including in patients with PD-L1 CPS<5.

The first-line Osemitamab (TST001) plus Nivolumab and CAPOX for advanced G/GEJ cancer results of Cohort G Phase I/IIa data will be featured as a poster presentation (Abstract # 4048) on June 1, 2024 at the ASCO 2024 Annual Meeting in Chicago, IL USA.

"These Phase II results mark a significant milestone for Osemitamab (TST001) as this data continues to demonstrate significant anti-tumor activities, particularly in patients with high or medium CLDN18.2 expression, including in those with PD-L1 CPS<5, which is consistent with our preclinical data and mechanistic hypothesis," said Dr. Caroline Germa, Executive Vice President, Global Medicine Development and Chief Medical Officer at Transcenta. "In this population, the triple combo treatment delivered significantly better PFS benefits than that of the doublet combinations of checkpoint inhibitor/chemo or CLDN18.2 targeted antibody plus chemo. These results further validate our strategy for the Global Phase III trial, which received FDA and CDE clearance and continue to advance the progression of Osemitamab (TST001) toward becoming a global therapy that elevates the current standard of care for HER2-negative metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma."

"I am excited about these results and the potential they hold for improving the first-line treatment effect and prolonger PFS and OS for patients with HER2-negative metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma," said Professor Lin Shen, Director, department of Gastrointestinal Oncology and Phase I Clinical Trial Center at Peking University Cancer Hospital; and Principal Investigator of the trial. "We look forward to sharing more detailed data at the upcoming ASCO 2024 Annual Meeting."

A brief summary of the study is as follows:

Study Design

Cohort G from TranStar102 study (NCT04495296) was designed to explore the safety and efficacy of Osemitamab (TST001) plus Nivolumab and CAPOX as the first-line treatment in advanced G/ GEJ cancer, with a safety lead-in and expansion phase. Eligible patients include HER2 negative or unknown, unresectable locally advanced or metastatic G/GEJ cancer, regardless of CLDN18.2 or PD-L1 expression. CLDN18.2 and PD-L1 status are analyzed retrospectively using Claudin 18.2 IHC 14G11 LDT assay and PD-L1 IHC 28-8 pharmDx at a central laboratory. The CLDN18.2 expression was divided into three subgroups: H/M (high/medium), L (low) and R (rest: lower or negative) according to the percentage of tumor cells showing membranous CLDN18.2 staining per Claudin 18.2 IHC 14G11 LDT assay.

Encouraging ORR and mPFS

As of the cut-off date, 82 patients had been dosed with a median follow-up of 12.6 months. Efficacy analysis was performed in the 66 patients with known CLDN18.2 and PD-L1 expression status. A clear trend between anti-tumor efficacy and CLDN18.2 expression level has been observed, with mPFS of 12.6 months in the patients with high or medium expression (H/M), 8.5 months in patients with low expression (L) and 6.7 months in the rest patients (R) respectively. Confirmed response rate was respectively 68%, 61.1% and 50% respectively.   Compared to the R group, the PFS Hazard Ratio (HR) of HM vs R is 0.443 (95% CI 0.205, 0.985), and HML vs R is 0.560 (95% CI 0.292, 1.074). The same trend was observed in patients with PD-L1 CPS<5 patients, and the mPFS of patients with CLDN18.2 H/M expression is 12.6 months too in this subgroup.

Manageable Safety Profile

The safety profile of the triplet is generally consistent with the safety data of Osemitamab (TST001)/CAPOX combination in 1L G/GEJ cancer patients presented previously (Journal of Clinical Oncology Volume 41, Issue 16, June 1, 2023, Abstract 4046). The main toxicities are on-target-off-tumor effects that are manageable, including nausea, hypoalbuminemia and vomiting, mostly grade 1 or 2.

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 (TranStar101/NCT04396821, TranStar102/NCT04495296). Osemitamab (TST001) has been 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.

About Transcenta

Transcenta (HKEX: 06628) is a clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing.

Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Princeton, US and in Beijing, Shanghai and Guangzhou of China, and External Partnering Center in Boston and Los Angeles, US. Transcenta has also initiated the construction of the Group Headquarters and the second high-end biopharmaceutical facility with ICB as its core technology in Suzhou Industrial Park. Transcenta is developing 13 therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders.

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