IBI-389 / Innovent Biologics - LARVOL DELTA

Safety and preliminary efficacy results of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: A phase 1 dose escalation and expansion study. (ASCO 2024) - P1 | "IBI389 showed manageable safety profiles in pts with advanced solid tumors and preliminary efficacy in CLDN18.2-positive pts with G/GEJ C."

Clinical • IO biomarker • P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CLDN18

Beyond Zolbetuximab: Next-Generation Targeting Strategies for CLDN18.2. (PubMed, J Gastrointest Cancer) - "Tissue immunohistochemistry remains the reference method for treatment selection; circulating tumor DNA cannot currently reproduce membranous protein intensity or spatial distribution, and liquid-biopsy approaches for CLDN18.2 reassessment remain investigational."

Journal • Review • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Hematological Disorders • Oncology • Solid Tumor • CLDN18

An integrated preclinical platform for comprehensive evaluation of T-Cell engagers (AACR 2026) - "AMG509 (targeting STEAP1), AMG757 (targeting DLL3), and IBI-389 (targeting CLDN18.2) were evaluated in models of prostate cancer, small-cell lung cancer, and patient-derived xenografts (PDX), respectively. In the BALB/c-hCD3EDG syngeneic model, administration of the CD3/CD20 bispecific antibody led to 81.5% tumor growth inhibition after 18 days.GemPharmatech's integrated strategy—combining in vitro screening with a range of in vivo models such as NCG, NCG-MHC-dKO, and CD3-humanized mice—enables rapid, scalable, and translationally relevant assessment of T-cell engager candidates. This comprehensive platform supports robust and efficient immuno-oncology drug discovery and development."

IO biomarker • Preclinical • Gastric Cancer • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Oncology • Pancreatic Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • CD3D • CD3E • CD3G • CLDN18 • DLL3 • STEAP1

VTS208: A first-in-class CD3/CLDN18.2/CDH17 Tri-specific T cell engager (TCE) for the treatment of gastrointestinal (GI) cancer (AACR 2026) - "Zolbetuximab (Astellas' anti-CLDN18.2 mAb, approved) has validated CLDN18.2 as a promising tumor-associated antigen (TAA) for gastrointestinal (GI) cancer therapy. CLDN18.2-targeting T cell engagers (TCEs), including IBI389 (phase I) and ASP2138 (phase I), demonstrate anti-tumor activity in patients with low CLDN18.2 expression, indicating that the TCE modality is effective even with minimal TAA expression...Current development includes CMC process optimization and dose-range-finding (DRF) toxicity studies. With mini-pool fermentation titers of 4-6 g/L supporting targeted drug substance concentrations for subcutaneous administration, the IND application is scheduled for filing in H2 2026.In summary, VTS208's unique trispecific design and differentiated features demonstrate promising efficacy and safety, positioning it as a compelling first-in-class TCE candidate for clinical development."

Trispecific • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CDH17 • CLDN18

The claudin-18.2-CD3 bispecific antibody IBI389 exerts an antitumor effect on malignant tumors with positive claudin-18.2 expression by promoting T-cell infiltration and remodeling the tumor immune microenvironment. (PubMed, Transl Cancer Res) - "In this study, we demonstrated that IBI389 effectively redirects T cells to CLDN18.2-expressing tumors, suppresses tumor growth, and synergizes with PD-1 blockade and has a favorable safety profile. By virtue of its ability to enhance immune infiltration, remodel cytokine responses, and reduce tumor-immune spatial separation, IBI389 may have considerable potential as a novel therapeutic strategy for CLDN18.2-positive gastric cancer and related malignancies."

IO biomarker • Journal • Gastric Cancer • Immune Modulation • Immunology • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • CLDN18 • IFNG • IL10 • IL17A • IL4 • TNFA

STING agonist ADU-S100 improves the antitumor response of CLDN18.2/CD3 BiTEs by enhancing stem-like tumor-reactive CD8+ T cells in pancreatic adenocarcinoma (AACR 2024) - "By qPCR, western blot and flow cytometry, an orthotopic transplantation mouse model of pancreatic cancer and an in vitro tumor-PBMC coculture system were established to reveal the potential molecular mechanism of STING agonist ADU-S100 in optimizing the effects of CLDN18.2/CD3 BiTEs (IBI389). In PDAC organoids, IBI389 induced potent, specific cytotoxicity, the CLDN18.2 BiTEs significantly engaged human CD3+ T cells with tumor cells in an organoid-PBMC coculture system in vitro, resulting in the formation of the immunological synapse (IS). Pancreatic tumors appear to evade immune response by inducing immune-suppressive tumor microenvironment development. In mice, the combination of STING agonist ADU-S100 and CLDN18.2 BiTEs increased the proportion of memory and stem-like CD4+ and CD8+ T cells while decreasing the proportion of regulatory and exhausted T cells in pancreatic tumors, eradicating all detectable tumors. This data may be utilized to formulate immune-based..."

Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD8 • CLDN18 • HAVCR2 • IL2RA • IL7R • ISG20 • PD-1

Safety and preliminary efficacy results of IBI389, an anti-Claudin18.2×CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: a phase 1 dose escalation and expansion study. (PubMed, BMC Med) - P1 | "IBI389 showed manageable safety profiles in patients with advanced solid tumors and preliminary efficacy in Claudin18.2-positive patients with GC/GEJC."

Journal • P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Hematological Disorders • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CLDN18

Innovent Reports Oncology Pipeline Updates at Investor Meeting (PRNewswire) - P1a/b | N=210 | NCT05458219 | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "The world's first ADC single agent to show breakthrough efficacy in pancreatic cancer: Preliminary Phase 1 data of IBI343 in pancreatic cancer patients who had received at least one line of treatment showed that the objective response rate (ORR) was 40% in CLDN18.2 IHC1/2/3+≥60% pancreatic cancer patients (n=10) who received 6 mg/kg IBI343....Based on the unique advantages of IBI343 and IBI389 demonstrated in early clinical trials, Innovent is advancing the development of IBI343 for the MRCT Phase 3 clinical trial in gastric cancer. Additionally, the Company is moving forward with proof-of-concept clinical studies of both IBI343 and IBI389 in the difficulty-to-treat pancreatic cancer."

P1 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Safety and efficacy of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with advanced pancreatic ductal adenocarcinoma: Preliminary results from a phase 1 study. (ASCO 2024) - P1 | "IBI389 showed manageable safety profiles in pts with advanced PDAC. Preliminary efficacy was observed, including in pts with relatively low expression of CLDN18.2."

Clinical • IO biomarker • Metastases • P1 data • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CLDN18

Innovent Delivers Oral Presentations at the 2024 ASCO Annual Meeting on Clinical Data of First-in-Class anti-CLDN18.2/CD3 Bispecific Antibody (IBI389) for the Treatment of Advanced Pancreatic Cancer and Gastric Cancer (PRNewswire) - P1a/1b | N=320 | NCT05164458 | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "Innovent Biologics...delivered two oral presentations of its first-in-class anti-CLDN18.2/CD3 bispecific antibody...at the 2024...ASCO Annual Meeting....Abstract#: 4011: As of March 11, 2024, a total of 72 subjects with advanced unresectable or metastatic pancreatic ductal adenocarcinoma have received IBI389 monotherapy....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%."

P1 data • Pancreatic Ductal Adenocarcinoma

Innovent Delivers Oral Presentations at the 2024 ASCO Annual Meeting on Clinical Data of First-in-Class anti-CLDN18.2/CD3 Bispecific Antibody (IBI389) for the Treatment of Advanced Pancreatic Cancer and Gastric Cancer (PRNewswire) - P1a/1b | N=320 | NCT05164458 | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "Innovent Biologics...delivered two oral presentations of its first-in-class anti-CLDN18.2/CD3 bispecific antibody...at the 2024...ASCO Annual Meeting....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."

P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

Clinical trials of CD3/CLDN18.2 dual antibodies launched in China; latest data on IBI389 for the treatment of pancreatic cancer and gastric cancer released [Google translation] (new.qq.com) - P1 | N=320 | NCT05164458 | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "The Phase I clinical trial data for pancreatic cancer and gastric cancer patients will be released at the 2024 ASCO conference. The summary data was recently released....For patients with pancreatic cancer, the dose of IBI389 was 600ug/kg, and preliminary efficacy was observed in patients with CLDN18.2 expression ≥10% (immunohistochemistry 2+/3+). Among the 23 evaluable patients, 7 had PR and 9 had SD. The ORR was 30.4% and the DCR was 69.6%. The median DoR and PFS have not yet been reached. For gastric cancer, preliminary efficacy of IBI389 was observed in patients with CLDN18.2 expression ≥10%. In G/GEJ C patients who had previously received ≥2 lines of treatment, 8 patients had PR and 11 patients had SD after receiving IBI389 treatment at doses of 10ug/kg to 600ug/kg (n=26)."

P1 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Safety and Efficacy of IBI389 Single Agent, and in Combination With Sintilimab, in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=320 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Phase classification: P1a/1b ➔ P1 | Trial completion date: Apr 2024 ➔ Sep 2024 | Trial primary completion date: Dec 2023 ➔ Apr 2024

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18

Safety and Efficacy of IBI389 Single Agent, and in Combination With Sintilimab, in Patients With Advanced Malignancies (clinicaltrials.gov) - P1a/1b | N=320 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18

Innovent Announces First Patient Dosing of Claudin18.2/CD3 Bispecific Antibody IBI389 in Phase 1a/1b Clinical Trial for Advanced Solid Tumor (PRNewswire) - "Innovent Biologics...announced the first patient dosing for its proprietary recombinant bispecific antibody targeting Claudin18.2 and CD3 (R&D code: IBI389) in a Phase I clinical trial for the treatment of advanced malignancies. The study (NCT05164458) is an open, multicenter Phase 1a/1b study evaluating the safety, tolerability and efficacy of IBI389 monotherapy or combination therapy in the treatment of advanced solid tumors."

Trial status • Oncology • Solid Tumor