On June 2, 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 two oral presentations of its first-in-class anti-CLDN18.2/CD3 bispecific antibody (R&D code: IBI389) for the treatment of advanced pancreatic cancer (PDAC) and gastric or gastroesophageal tumors (G/GEJC) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from clinical data of a Phase I study (NCT05164458) (Press release, Innovent Biologics, JUN 2, 2024, View Source [SID1234643942]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Hui Zhou, Senior Vice President of Innovent Biologics, stated, "We are excited to share the latest clinical development progress of IBI389 at ASCO (Free ASCO Whitepaper). Different from monoclonal antibodies, IBI389 redirects T cells to tumor cells by binding both CLDN18.2 expressed on tumor cells and CD3 on T cells, inducing T cell-mediated cell killing. Preclinical results showed that IBI389 could bind to tumor cells and exhibit significant anti-tumor effects even in cell lines with low CLDN18.2 expression. In the presented clinical data, IBI389 has shown promising efficacy in advanced G/GEJ tumors and PDAC, including those subjects with low and moderate CLDN18.2 expression. Notably, IBI389 is the world’s first bispecific antibody targeting CLDN18.2/CD3 to show encouraging efficacy signal in PDAC, representing a breakthrough for innovative treatments in difficult-to-treat cancers. We will continue to advance the clinical development of IBI389 for the benefit of more cancer patients."

Safety and Efficacy of IBI389 in Patients with Advanced Pancreatic Ductal Adenocarcinoma: Preliminary Results from the Phase I Study

Abstract#: 4011

As of March 11, 2024, a total of 72 subjects with advanced unresectable or metastatic pancreatic ductal adenocarcinoma have received IBI389 monotherapy. All subjects had received at least one prior systemic treatment, and 55.6% of the subjects had received two or more prior lines of systemic therapy.

The results showed that:

In subjects with CLDN18.2 IHC 2/3+≥10%, signs of efficacy were observed when treated with 100 μg/kg.
The recommended phase 2 dose (RP2D) 600 μg/kg group shows superior efficacy. 27 subjects have performed at least one post-baseline tumor evaluation, the objective response rate (ORR) was 29.6% (95%CI: 13.8-50.2), the confirmed objective response rate (cORR) was 25.9% (95%CI：11.1-46.3), and the disease control rate (DCR) was 70.4% (95%CI：49.8-86.2). Among the 18 subjects with CLDN18.2 IHC 2/3+≥40%, the cORR was 38.9% (95%CI：17.3-64.3).
As of May 1, 2024, the median progression-free survival (PFS) follow-up time was 4 months, and the median PFS was not yet mature, with a 3-month PFS rate of 57.1%.
Safety was similar to that of the overall population, and no new safety signals were observed.
Professor Jihui Hao, Tianjin Medical University Cancer Institute & Hospital, said, "Pancreatic cancer is one of the most aggressive malignancies with poor prognosis, and the incidence continues to increase. Currently, the standard treatment for most patients with metastatic pancreatic cancer is systemic chemotherapy. In the second-line treatment, the clinical options are very limited and primarily involving a different chemotherapy from the first-line regimen. The response rate to second-line chemotherapy is only 6%~16%, and the median survival time is only about 3~6 months [1,2]. Therefore, there is a great unmet clinical need for patients who have failed standard treatment. Studies have shown that the expression of CLDN18.2 in pancreatic cancer patients is up to 50%~70% [3], making it a potential novel target for therapy. IBI389 is the first bispecific antibody targeting CLDN18.2/CD3 that reported clinical data, and showed positive efficacy signals in patients with advanced pancreatic cancer. I hope the clinical exploration of this innovative drug could drive the progress in pancreatic cancer treatment."

Safety and Preliminary Efficacy Outcomes of IBI389 in Patients with Advanced Solid Tumors and Gastric or Gastroesophageal Tumors: A Phase I Dose Escalation and Expansion Study

Abstract#: 2519

This Phase I study is designed to evaluate the safety, tolerability, and preliminary efficacy of IBI389 in subjects with advanced solid tumors and G/GEJ tumors.

The results showed that:

As of May 1, 2024, 26 G/GEJC subjects with CLDN18.2 IHC 2/3+≥10% received ≥ 10 μg /kg IBI389 monotherapy and performed at least one post-baseline tumor evaluation, of which 8 subjects achieved partial response (PR); the objective response rate (ORR) and disease control rate (DCR) were 30.8% and 73.1%, respectively.
In terms of safety, as of March 11, 2024, a total of 120 subjects with advanced solid tumor malignancies who had previously failed or were intolerant to standard therapy were enrolled. IBI389 was generally well tolerated, and no dose-limiting toxicity (DLT) events were observed in each dose group. Cytokine release syndrome (CRS) occurred in 60% of subjects, and only one case developed grade 3. No grade 4 or 5 CRS happened. 58.3% subjects occurred ≥ grade 3 treatment-related adverse events (TRAEs). The most common ≥ grade 3 TRAEs were increased gamma-glutamyl transferase (21.7%), decreased lymphocyte count (13.3%) and decreased appetite (5. 0%）.
Professor Feng Bi, West China Hospital of Sichuan University, said, "Gastric cancer is one of the most common malignant tumors in the world, ranking the 5th most common malignant tumors, and the 4th leading cause of cancer death worldwide [4]. Single-agent chemotherapy is the main second-line treatment for advanced gastric cancer. Multiple studies have shown that the PFS of second-line single-agent chemotherapy is 2.0~4.1 months, and the OS was only 5.3~9.5 months, with limited clinical benefit [5]. In recent years, CLDN18.2 has gained the most attention as a therapeutic target in the field of gastrointestinal tumors, and studies have shown that the expression rate of CLDN18.2 in gastric cancer patients is 40%-87% [6]. Preliminary efficacy results from several studies show that this target has high druggability potential. In this study, IBI389 has demonstrated encouraging preliminary efficacy and tolerable safety in patients with advanced gastric tumors, suggesting the possibility of further exploration in this indication."

About IBI389 (anti-CLDN18.2/CD3 bispecific antibody)

IBI389 is an anti-CLDN18.2 T cell-engaging bispecific antibodies developed by Innovent Biologics. It induces immune synapse formations by linking CD3 molecules in T-cell receptor complexes and CLDN18.2 antigens on the surfaces of tumor cells. Therefore, IBI389 stimulates T-cell activation, resulting in cytolytic protein production, inflammatory cytokine release and further T-cell proliferation, which eventually leads to durable anti-tumor effects. Based on urgent clinical needs, Innovent has conducted clinical studies to explore the efficacy and safety of IBI389 as a monotherapy or in combination with various advanced malignancies.