Innovent Presents Clinical Data on IBI389 at 2024 ASCO for Pancreatic and Gastric Cancer

Innovent Biologics, Inc., a prominent biopharmaceutical company known for its innovative treatments for various major diseases, announced significant findings of its anti-CLDN18.2/CD3 bispecific antibody, IBI389, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The study, identified as Phase I (NCT05164458), focused on evaluating IBI389's efficacy for advanced pancreatic cancer (PDAC) and gastric or gastroesophageal tumors (G/GEJC).

Dr. Hui Zhou, Senior Vice President of Innovent, highlighted the uniqueness of IBI389. Unlike traditional monoclonal antibodies, IBI389 simultaneously binds to CLDN18.2 on tumor cells and CD3 on T cells, prompting T cell-mediated tumor cell destruction. Preclinical studies indicated that IBI389 could effectively engage tumor cells with low levels of CLDN18.2. Clinical data presented showed promising results in treating both advanced G/GEJ tumors and PDAC, even in patients with low to moderate CLDN18.2 expression. IBI389 stands as the first bispecific antibody targeting CLDN18.2/CD3 to demonstrate potential efficacy in PDAC, marking a breakthrough in treating challenging cancers. Dr. Zhou affirmed Innovent's commitment to advancing IBI389's clinical development to benefit more cancer patients.

Safety and Efficacy in Pancreatic Ductal Adenocarcinoma (PDAC)

Preliminary results from the Phase I study on advanced PDAC were shared. By March 11, 2024, 72 patients with advanced, unresectable, or metastatic PDAC had received IBI389 monotherapy. All had undergone at least one prior systemic treatment, with 55.6% having received two or more prior therapies.

Key findings included:
- For patients with CLDN18.2 IHC 2/3+≥10%, efficacy was observed at a 100 μg/kg dosage.
- The recommended Phase 2 dose (RP2D) of 600 μg/kg showed superior efficacy. Among 27 patients evaluated post-baseline, the objective response rate (ORR) was 29.6%, the confirmed ORR (cORR) was 25.9%, and the disease control rate (DCR) was 70.4%. For 18 subjects with CLDN18.2 IHC 2/3+≥40%, the cORR was 38.9%.
- As of May 1, 2024, the median progression-free survival (PFS) follow-up was four months, with a three-month PFS rate of 57.1%.

Safety outcomes were consistent with the overall population, without new safety signals.

Insights from Experts

Professor Jihui Hao from Tianjin Medical University Cancer Institute & Hospital emphasized the aggressive nature of pancreatic cancer and the limited efficacy of current second-line chemotherapy options. With CLDN18.2 expression in 50%-70% of pancreatic cancer patients, IBI389 offers a novel therapeutic target. The promising clinical data on IBI389 suggests it could significantly impact the treatment landscape for pancreatic cancer.

Safety and Efficacy in Gastric/Gastroesophageal Tumors

The Phase I study also evaluated IBI389 in advanced solid tumors and G/GEJC. By May 1, 2024, 26 G/GEJC patients with CLDN18.2 IHC 2/3+≥10% who had undergone at least one post-baseline tumor evaluation showed an ORR of 30.8% and a DCR of 73.1%.

Regarding safety, by March 11, 2024, 120 subjects with advanced solid tumors had been treated. IBI389 was generally well tolerated, with no dose-limiting toxicities observed. While cytokine release syndrome (CRS) occurred in 60% of subjects, only one case was grade 3, and no cases reached grades 4 or 5. The most common ≥ grade 3 treatment-related adverse events (TRAEs) included increased gamma-glutamyl transferase (21.7%), decreased lymphocyte count (13.3%), and decreased appetite (5.0%).

Expert Commentary

Professor Feng Bi from West China Hospital of Sichuan University noted that gastric cancer is among the most prevalent and deadly cancers globally. Current second-line treatments offer limited benefits. The high expression rate of CLDN18.2 in gastric cancer patients makes it a valuable therapeutic target. Preliminary efficacy results from IBI389 suggest significant potential for further exploration in treating advanced gastric tumors.

About IBI389

IBI389 is an anti-CLDN18.2 T cell-engaging bispecific antibody developed by Innovent Biologics. It links CD3 molecules in T-cell receptor complexes with CLDN18.2 antigens on tumor cells, stimulating T-cell activation and cytotoxic activity against tumor cells. Innovent is committed to exploring the monotherapy and combination therapy potential of IBI389 in various advanced malignancies.

About Innovent Biologics

Founded in 2011, Innovent Biologics aims to provide affordable, high-quality biopharmaceuticals for patients globally. The company focuses on discovering, developing, manufacturing, and commercializing treatments for cancer, cardiovascular and metabolic disorders, autoimmune diseases, and ophthalmology. Innovent has launched ten products, with several others in various stages of regulatory review and clinical trials. Partnering with over 30 global healthcare companies, Innovent strives to make advanced pharmaceutical drugs widely accessible.

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