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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