On June 1, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported Phase 1 clinical data of IBI343 (TOPOi anti-CLDN18.2 ADC) for the treatment of advanced pancreatic ductal adenocarcinoma or biliary tract cancer at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (NCT05458219) (Press release, Innovent Biologics, JUN 1, 2024, View Source [SID1234643951]). In addition, clinical data of the treatment for advanced gastric or gastroesophageal tumors from this Phase 1 trial will be published in oral presentation at the ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2024 this month.

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Dr. Hui Zhou, Senior Vice President of Innovent Biologics, said, "We are excited to share the latest clinical development updates on IBI343 at ASCO (Free ASCO Whitepaper). As an innovative TOPOi ADC, IBI343 showed a positive clinical signal in subjects with advanced pancreatic cancer and the incidence of grade 3 or above gastrointestinal adverse events is low. It is the first CLDN18.2 ADC to achieve a breakthrough in this difficult-to-treat cancer and shed light on the exploring directions to this therapeutic field. We will continue to follow up on the clinical data update of IBI343. As one of the few biopharmaceutical companies with leading R&D capabilities in both immunotherapy (IO) and antibody-drug conjugates (ADCs), we will also explore combination therapy of IBI343 and its therapeutic potential in other solid tumors such as gastric cancer for the benefit of more patients."

Safety and efficacy of IBI343 (anti-CLDN18.2 ADC) in patients with advanced pancreatic ductal adenocarcinoma or biliary tract cancer: preliminary results from a Phase I study

Abstract#:3037

This Phase I study is conducted in China and Australia, aiming to evaluate the safety, tolerability and preliminary efficacy of IBI343 in subjects with advanced solid tumors. Data on patients with advanced pancreatic ductal adenocarcinoma or biliary tract cancer were presented at this congress. As of December 19, 2023, a total of 35 patients with advanced pancreatic ductal adenocarcinoma (PDAC) or biliary tract cancer (BTC) were enrolled, and all subjects had received at least one prior systemic treatment, with a median of 2 lines of treatment.

The results showed that:

As of January 15, 2024, 25 subjects had performed at least one post-baseline tumor evaluation. 7 subjects achieved partial response (PR), 5 of which were PDAC patients, 2 were BTC patients. The objective response rate (ORR) was 28.0% (95% CI: 12.1-49.4), and the disease control rate (DCR) was 80.0% (95% CI: 59.3-93.2).
In the 6 mg/kg dose group, 13 subjects with CLDN18.2 1/2/3+≥60% had at least one post-baseline tumor assessment, of which 5 achieved PR with an ORR of 38.5% (95%CI: 13.9-68.4) and a DCR of 84.6% (95% CI：54.6-98.1). Among the 10 subjects with advanced PDAC in this subgroup, the ORR was 40% (95% CI: 12.2-73.8). DoR and PFS data are not mature yet.
In terms of safety, 80.0% of subjects experienced treatment-related adverse events (TRAEs). Common TRAEs were anemia (42.9%), neutrophil count decreased (28.6%), nausea (25.7%), vomiting (25.7%) and white blood cell count decreased (22.9%). 25.7% of participants developed ≥ grade 3 TRAEs. No TRAE led to death.
Professor Xianjun Yu, Fudan University Shanghai Cancer Center, said: "Advanced pancreatic cancer and biliary tract cancer progress rapidly while the clinical course is initially insidious. Most patients are often not diagnosed until advanced stages with poor prognosis. Currently, chemotherapy remains a mainstay of the first-and-second line treatments for advanced pancreatic cancer and bile duct cancer. The clinical options for second-line treatment are particularly limited and cannot bring significant clinical benefits to patients. FOLFOX is used as a second-line standard of care for advanced biliary tract cancer with an ORR of 5%, a median overall survival OS of 6.2 months [1]. In the second-line treatment of pancreatic cancer, the response rate to chemotherapy is only 6%~16%, and the median survival time is only about 3~6 months [2].

CLDN18.2 has become a promising target for the treatment of patients with digestive malignancies, which has a high expression rate in pancreatic cancer and biliary tract cancer. The expression rate in pancreatic cancer patients is 50%~70% [3], and 52% of biliary tract cancer [4]. Promising clinical benefit of the novel TOPOi anti-CLDN18.2 ADC IBI343 has been observed in subjects with advanced pancreatic cancer and biliary tract cancer. Particularly in advanced pancreatic cancer participants with high CLDN18.2 expression, it showed encouraging efficacy signals and a tolerable safety profile, which may bring patients novel and effective treatment options."

About IBI343（Anti CLDN18.2 ADC）

IBI343 is a recombinant human anti-Claudin 18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization will occur and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect".

As an innovative TOPOi ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in this phase I clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric cancer and pancreatic cancer. In May 2024, The National Medical Products Administration (NMPA) of China granted breakthrough therapy designation (BTD) to IBI343 for use as a single agent in patients with claudin 18.2–positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who experienced disease progression following 2 prior lines of systemic treatment. The multi-center Phase 3 trial of IBI343 for this indication is in preparation.