Nature Medicine Published Phase 1 Results of Innovent Biologics' Anti-CLDN18.2 ADC (IBI343) in Patients with Advanced Gastric/Gastroesophageal Junction Adenocarcinoma
Rhea-AI Summary
Innovent Biologics (OTC:IVBIY) announced the publication of Phase 1 clinical trial results for IBI343, their innovative anti-CLDN18.2 ADC, in Nature Medicine. The study focused on treating advanced gastric/gastroesophageal junction adenocarcinoma.
Key findings include a confirmed ORR of 32.3% at 6 mg/kg dose and 47.1% at 8 mg/kg dose in patients with high CLDN18.2 expression. The median PFS was 5.5 months for the 6 mg/kg group and 6.8 months for the 8 mg/kg group. The treatment showed manageable safety profile with 66.4% of patients experiencing grade ≥3 TEAEs.
Based on these promising results, Innovent has launched a multi-regional Phase 3 clinical trial (G-HOPE-001, NCT06238843) to further evaluate IBI343's efficacy.
Positive
- Strong efficacy with 47.1% confirmed ORR at 8 mg/kg dose in high CLDN18.2 expression patients
- Publication in prestigious Nature Medicine (Impact Factor: 58.7) validates clinical potential
- Manageable safety profile with very few grade ≥3 gastrointestinal adverse events
- Advancement to Phase 3 multi-regional clinical trial indicates development progress
Negative
- 66.4% of patients experienced grade ≥3 treatment-emergent adverse events
- Overall survival data not yet mature for full assessment
- Limited duration of response with median of 5.6-5.7 months across dose groups
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SAN FRANCISCO and SUZHOU, China, July 16, 2025 /PRNewswire/ -- 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, announced that Nature Medicine (IF: 58.7) has published the results of the Phase 1 clinical study of IBI343, an innovative anti-CLDN18.2 ADC, for the treatment of advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma[Link]. Publication in this leading international academic journal indicates the strong recognition of the therapy's clinical potential and marks another significant milestone in
Gastric cancer remains one of the most common malignant tumors in the world. According to the GLOBOCAN 2022 statistics, it ranks as the fifth most common malignant tumor and the fifth leading cause of cancer-related death globally, with an estimated 970,000 new cases and 660,000 deaths annually. Each year,
CLDN 18.2 is a tight junction protein expressed in differentiated epithelial cells on the gastric mucosa under normal physiological conditions. Previous studies have revealed that Claudin18.2 is highly expressed in multiple types of cancer, including gastric cancer (60
This published study is a global, multicenter Phase 1 clinical trial (ClinicalTrial.gov identifier: NCT05458219) designed to evaluate the safety, tolerability and preliminary efficacy of IBI343 in patients with advanced solid tumors. Between October 26, 2022, and June 30, 2024, a total of 116 subjects with advanced G/GEJ adenocarcinoma were enrolled to receive IBI343 monotherapy (8 in escalation and 108 in expansion).
IBI343 has demonstrated encouraging tumor response and survival benefit
The study analyzed the efficacy data of evaluable subjects with high expression of CLDN18.2 (≥
- At 6 mg/kg (N=31), 15 patients had partial responses (PR) including 9 patients with confirmed PRs and 1 patient awaiting confirmation. The confirmed ORR was
29.0% (95% CI: 14.2-48.0) and the disease control rate (DCR) was90.3% (95% CI: 74.2-98.0). In 9 patients with confirmed response, the median duration of response (DoR) was 5.6 months (95% CI: 2.8-7.0). The median follow-up was 10.6 months (95% CI: 9.7-11.5) for PFS and OS. The median PFS was 5.5 months (95% CI: 4.1-7.0). OS data was not mature with the current median OS of 10.8 months (95% CI: 6.8-NC). After data cutoff, response of the remaining 1 patient was confirmed on July 26, 2024 and the confirmed ORR was updated to32.3% (95% CI: 16.7-51.4). - At 8 mg/kg (N=17), 17 patients with high expression of CLDN 18.2 were evaluable. Among them, 9 patients had PRs including 8 patients had confirmed PR. The confirmed ORR
47.1% (95% CI: 23.0-72.2), and the DCR was88.2% (95% CI: 63.6-98.5). In eight patients with confirmed response, the median DoR was 5.7 months (95% CI: 2.7-NC). Of all G/GEJ adenocarcinoma patients with high CLDN18.2 expression treated at 8 mg/kg (N=19, including 1 patient from dose escalation and 18 patients from dose expansion), the median follow-up was 8.1 months (95% CI: 7.6-8.5) for PFS and OS. The median PFS was 6.8 months (95% CI: 2.8-7.5), and the median OS was not reached with events occurred in36.8% patients.
IBI343 also demonstrated superior safety
- Among all patients with G/GEJ adenocarcinoma (n=116, including 8 patients with gastric cancer from the dose escalation phase),
66.4% patients (77/116) had ≥3 grade TEAEs. The most common ≥3 grade TEAEs (≥35% ) were neutrophil count decreased (28.4% ), white blood cell count decreased (25.9% ), and anemia (16.4% ). There were very few grade ≥3 gastrointestinal adverse events, including only1.7% of grade ≥3 nausea. No interstitial lung disease of any grade was reported. Treatment-related toxicity was alleviated with adequate supportive treatment, and the overall safety was tolerable.
Integrated pharmacokinetics (PK), exposure-response, safety, and efficacy data supported 6 mg/kg Q3W as the recommended Phase 2 dose (RP2D) of IBI343. This provides support for the conduct of subsequent Phase 3 trial, suggesting that IBI343 may become a new treatment option for patients with gastric cancer in the future.
Professor Lin Shen, Corresponding Author, Leading Principal Investigator, from Beijing Cancer Hospital, said, "Following the eras of chemotherapy, targeted therapy and immunotherapy, ADCs have opened a new frontier in the treatment of gastrointestinal tumors. IBI343 is a new generation of Fc-silent anti-CLDN18.2 ADC that has shown encouraging clinical benefits and low gastrointestinal toxicity in Phase 1 studies. We look forward to the results of the Phase 3 study comparing IBI343 with standard treatment, aiming to ultimately reshape clinical practice, transform treatment paradigms, and usher in a new chapter in precision medicine."
Dr. Hui Zhou, Chief R&D Officer for Oncology Pipeline at Innovent Biologics, said, "There is a huge unmet clinical need for the treatment of advanced gastric cancer. The Phase 1 study results of IBI343 in advanced gastric and gastroesophageal junction adenocarcinoma, now published in the top international journal, Nature Medicine, further verify the clinical value of IBI343 in this population. We will work with researchers worldwide to advance the multi-regional Phase 3 clinical trial (G-HOPE-001), with the goal of establishing a new paradigm in clinical diagnosis and treatment and ultimately benefiting gastric cancer patients around the world. We are also exploring the therapeutic potential of IBI343 in pancreatic cancer and other indications."
About Gastric/ Gastroesophageal Junction Adenocarcinoma
Gastric cancer is one of the most prevalent malignant tumors worldwide and a leading cause of cancer-related deaths globally. The 5-year survival rate of patients with metastatic gastric cancer is less than
Claudin, a member of the tight junction molecule family, is a key structural and functional component of epithelial tight junctions. Among them, CLDN18.2 is normally buried in gastric mucosa, but the development of malignancy leads to disruption of tight junctions and exposure of CLDN18.2 epitopes on the membrane of tumor cells[iv]. CLDN18.2 is expressed in up to
About IBI343（Anti CLDN18.2 ADC）
IBI343 is a recombinant human anti-CLDN18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. It specifically binds to the tumor cells expressing CLDN18.2, triggering CLDN18.2-dependent internalization of the ADC. Once inside the cell, the cytotoxic payload is released, resulting in DNA damage and ultimately apoptosis of the tumor cells. The released drug can also diffuse across the plasma membrane to reach and kill neighboring cells, resulting in a "bystander killing effect".
As an innovative TOPO1i ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in this Phase 1 clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric cancer and pancreatic cancer.
The multi-regional Phase 3 clinical trial of IBI343 for advanced gastric / gastroesophageal junction adenocarcinoma is now recruiting patients (G-HOPE-001, NCT06238843). The relevant indication has been granted Breakthrough Therapy Designation (BTD) by
The multi-regional Phase 1 clinical trial of IBI343 for advanced pancreatic ductal adenocarcinoma is also enrolling patients (NCT05458219). This indication has received Fast Track Designation (FTD) from the
About Innovent Biologics
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 16 products in the market. It has 2 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center.
Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.
Statement:
1.Innovent Biologics does not recommend the use of unapproved drugs/indications. |
2.Ramucirumab injection (Cyramza®), selpercatinib capsules (Retsevmo®) and pirtobrutinib tablets (Jayprica®) were developed by Eli Lilly and Company |
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References
[i] Lasithiotakis K, Antoniou SA, Antoniou GA, Kaklamanos I, Zoras O. Gastrectomy for stage IV gastric cancer. a systematic review and meta-analysis. Anticancer Res. May 2014;34(5):2079-85 |
[ii] Xu B, Wang JM. Epidemiological study of gastric cancer[J]. Chin J Cancer Prev Treat, 2006,13(1): 81-87. |
[iii] Chan WL, Lam KO, So TH, et al. Third-line systemic treatment in advanced/metastatic gastric cancer: a comprehensive review. Ther Adv Med Oncol. 2019;11:1758835919859990. |
[iv] Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008;14(23):7624-7634. |