arcotatug tavatecan (IBI-343) / Innovent Biologics, Takeda - LARVOL DELTA

IBI343 Combined with Sintilimab and SOX as First-Line Therapy for CLDN18.2-Positive Locally Advanced Unresectable or Metastatic HER2-Negative Gastric/Gastroesophageal Junction Adenocarcinoma (G/GEJ AC) (ESMO Asia 2025) - No abstract available

Clinical • Metastases • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • HER-2

Antibody-drug conjugates targeting the cadherin, claudin and nectin families of adhesion molecules. (PubMed, Front Mol Med) - "Enfortumab vedotin is an NECTIN4-targeting antibody-drug conjugate that is approved for the treatment of urothelial cancer, whereas other ADCs or derivatives that target NECTIN4, such as bulumtatug fuvedotin, SHR-A2102 and zelenectide pevedotin, are being studied in randomized phase III clinical trials. In contrast, arcotatug tavatecan, garetatug rezetecan, sonesitatug vedotin and tecotabart vedotin are anti-CLDN18.2 ADCs in phase III clinical trials for the treatment of CLDN18.2-positive gastric or gastroesophageal junction adenocarcinomas, and raludotatug deruxtecan is an anti-CDH6 ADC in a phase II/III clinical trial for the treatment of platinum-resistant ovarian cancer. ADCs that target cell-cell adhesion molecules are a rapidly emerging class of cancer therapeutics, and bispecific ADCs and longitudinal companion diagnostics are emerging to further improve the clinical benefits of conventional ADCs."

Journal • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer • CDH17 • CDH6 • CLDN18 • CLDN6

IBI343 (CLDN18.2 ADC): Global License for Development and Commercialization (PRNewswire) - "Innovent will grant Takeda exclusive global rights to develop, manufacture and commercialize IBI343 outside of Greater China. Takeda plans to advance the development of IBI343 and expand into first-line gastric and pancreatic cancer settings. Takeda will make potential milestone payments, and tiered royalties on net sales up to high-teens for the license of IBI343."

Licensing / partnership • Gastric Cancer • Pancreatic Cancer

IBI343 Combined With Chemotherapy in Advanced Pancreatic Cancer (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: Zhejiang University | Not yet recruiting ➔ Recruiting | Initiation date: Jan 2025 ➔ Apr 2025

Enrollment open • Trial initiation date • Oncology • Pancreatic Cancer • Solid Tumor

G-HOPE-001: A Multicenter, Phase 3 Study of IBI343 Monotherapy Versus Treatment of Investigator's Choice in Subjects With Previously Treated, Claudin (CLDN) 18.2-positive, HER2-negative, Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Enrolling by invitation ➔ Recruiting

Enrollment status • Monotherapy • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

A Multicenter Study of IBI343 Monotherapy Versus Placebo in Subjects With Previously Treated, Claudin (CLDN) 18.2-positive, Pancreatic Cancer(G-HOPE-002) (clinicaltrials.gov) - P3 | N=201 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Oncology • Pancreatic Cancer • Solid Tumor

CLDN18.2-targeting antibody-drug conjugate IBI343 in advanced gastric or gastroesophageal junction adenocarcinoma: a phase 1 trial. (PubMed, Nat Med) - P1 | "IBI343 was well tolerated, with a manageable safety profile and promising efficacy in G/GEJ adenocarcinoma. Further research is required to understand optimal sequencing, and biomarker-informed combination therapy, in G/GEJ tumors given the development of multiple therapies targeting CLDN18.2 in addition to human epidermal growth factor receptor 2 and programmed cell death 1 ligand 1.ClinicalTrials.gov registration: NCT05458219 ."

Journal • P1 data • Esophageal Cancer • Febrile Neutropenia • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hematological Disorders • Interstitial Lung Disease • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • CLDN18 • HER-2 • PD-1 • PD-L1

Nature Medicine Published Phase 1 Results of Innovent Biologics' Anti-CLDN18.2 ADC (IBI343) in Patients with Advanced Gastric/Gastroesophageal Junction Adenocarcinoma (PRNewswire) - P1a/b | N=470 | NCT05458219 | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "Innovent Biologics...announced that Nature Medicine (IF: 58.7) has published the results of the Phase 1 clinical study of IBI343...for the treatment of advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma....A total of 116 subjects with advanced G/GEJ adenocarcinoma were enrolled....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) was 90.3% (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)."

P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

A Multicenter Study of IBI343 Monotherapy Versus Placebo in Subjects With Previously Treated, Claudin (CLDN) 18.2-positive, Pancreatic Cancer(G-HOPE-002) (clinicaltrials.gov) - P3 | N=201 | Not yet recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Monotherapy • New P3 trial • Oncology • Pancreatic Cancer • Solid Tumor

IBI343 Combined With Sintilimab Plus Chemotherapy in Gastric Cancer (clinicaltrials.gov) - P1/2 | N=55 | Recruiting | Sponsor: Ruijin Hospital

New P1/2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

A multiregional, randomized, controlled, open-label, phase 3 study of the anti-claudin18.2 (CLDN18.2) antibody-drug conjugate (ADC) arcotatug tavatecan (IBI343) in gastric or gastroesophageal junction adenocarcinoma (G/GEJA): Trial in progress. (ASCO 2025) - P3 | "Pts are randomized in a 1:1 ratio to receive IBI343 6mg/kg Q3W in the experimental arm or to receive treatment of investigator's choice including irinotecan, paclitaxel, or trifluridine/tipiracil in the control arm. The secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and time to response (TTR) per RECIST v1.1, quality of life (QoL), safety, pharmacokinetics (PK) and immunogenicity. The trial is currently enrolling pts in China and Japan."

Clinical • P3 data • Biliary Cancer • Biliary Tract Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CLDN18 • HER-2

Claudin18.2 (CLDN18.2) expression and efficacy in pancreatic ductal adenocarcinoma (PDAC): Results from a phase I dose expansion cohort evaluating IBI343. (ASCO 2025) - P1 | "IBI343 was well tolerated and continues to show encouraging efficacy in pts with PDAC. Efficacy benefit was most pronounced in those with CLDN18.2 expression ≥60%, suggesting that CLDN18.2 can be a predictive biomarker for response to IBI343 in PDAC. The trial is enrolling in Australia, China, and US."

Clinical • P1 data • Anemia • Hematological Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CLDN18

ASCO 2025 Oral Presentation: Innovent Biologics Announces Updated Data of IBI343 (Novel Anti-CLDN18.2 ADC) From the Phase 1 Clinical Study in Patients with Advanced Pancreatic Cancer (PRNewswire) - P1a/b | N=470 | NCT05458219 | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "...The updated results from the study's dose-expansion cohort were presented at the 2025 ASCO as follows: As of March 14, 2025, a total of 83 patients with pancreatic cancer had received at least one dose of IBI343 with a median follow-up time of 11.1 months. As the data cutoff date, in patients with CLDN18.2 1+2+3+≥60% expression treated at the 6mg/kg dose (N=44), the confirmed overall objective response rate (cORR) was 22.7% and the disease control rate (DCR) was 81.8%. The median progression-free survival (mPFS) was 5.4 months, and the median overall survival (mOS) was 9.1 months. Among them, 17 patients had received only one line of prior treatment, achieving a mPFS of 5.4 months and a mOS of 12.1 months; and 18 patients had received two lines of prior treatment, the mPFS was 5.3 months and the mOS was 9.1 months."

P1 data • Pancreatic Cancer

VBC108: a first-in-class CDH17/CLDN18.2 targeted bispecific antibody drug conjugate (ADC) to overcome tumor heterogeneity of gastrointestinal cancers (GC, PADC, CRC, etc.) (AACR 2025) - "However, these therapies face challenges due to the heterogeneous expression of CLDN18.2, leading to inconsistent efficacy and the need of patient stratification, as observed with Zolbetuximab, AZD0901 and IBI343. VBC108 also exhibited excellent developability in a comprehensive developability assessment (DA) test, making it a strong candidate for further CMC development. In summary, VBC108, with its unique design, shows the potential as a first-in-class ADC for GI cancer and supports the advancement to clinical trials."

Heterogeneity • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CDH17 • CLDN18

Seven Oral Presentations: Innovent to Present Breakthrough Clinical Data of IBI363（PD-1/IL-2α-bias）and Other Novel Drug Candidates at the 2025 ASCO Annual Meeting (PRNewswire) - "Innovent Biologics...announces that clinical data for its innovative bispecific antibodies and ADC molecules, including oral presentations for IBI363 (PD-1/IL-2α-bias) and IBI343 (CLDN18.2 ADC), will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2025 from May 30 to June 3, 2024, in Chicago, Illinois, U.S."

Clinical data • Trial status • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Mucosal Melanoma • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

IBI343 Combined with Chemotherapy in Advanced Pancreatic Cancer (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: Zhejiang University

New P2 trial • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

Innovent Receives NMPA Breakthrough Therapy Designation for IBI343 (Anti-CLDN18.2 ADC) as Monotherapy for Advanced Pancreatic Cancer (PRNewswire) - "Innovent Biologics...announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI343, a potentially best-in-class TOPO1i anti-CLDN18.2 ADC, as monotherapy for the treatment of CLDN18.2-positive advanced pancreatic ductal adenocarcinoma (PDAC) patients who have progressed after at least one line of prior systematic treatment. The BTD for IBI343 was granted based on data from an ongoing Phase 1 study conducted in China, Australia and the U.S. (NCT05458219), which demonstrated favorable safety and tolerability, as well as promising antitumor activity of IBI343 monotherapy in advanced PDAC patients."

Breakthrough therapy • Evidence highlight • Oncology • Pancreatic Ductal Adenocarcinoma • CLDN18

Domestic new drugs have a breakthrough!…Class I new drugs have been included in the breakthrough therapy [Google translation] (Sohu.com) - "On January 8, the official website of the China Food and Drug Administration (CDE) announced that four domestically produced Class I new drugs were to be included in the breakthrough therapy category, which attracted widespread attention...drugs are...YL201 (Yilian Biopharma), IBI343 (Innovent Biologics)...YL201, developed by Yilian Bio, is an antibody-drug conjugate (ADC) targeting B7-H3, mainly used to treat recurrent or metastatic nasopharyngeal carcinoma...Innovent Biologics' IBI343 is an ADC targeting CLDN18.2, developed specifically for advanced pancreatic ductal adenocarcinoma."

Breakthrough therapy • Nasopharyngeal Carcinoma • Pancreatic Ductal Adenocarcinoma

Innovent Presents Updated Data From Innovative Anti-CLDN18.2 ADC (IBI343) Phase 1 Study in Patients with Advanced Pancreatic Cancer at the ESMO Asia Congress 2024 (PRNewswire) - P1 | N=470 | NCT05458219 | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "Innovent Biologics... announced updated Phase 1 study results of IBI343...for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC) during an oral presentation at the ESMO Asia Congress 2024....As of September 6, 2024, a total of 43 patients with CLDN18.2-positive (≥60% tumor cells with membranous staining intensity ≥1+ by IHC) advanced PDAC received IBI343 6 mg/kg Q3W monotherapy. All participants had previously received at least 1 line of prior therapy, and 60.5% had received 2 or more lines of anticancer treatment. 43 patients were efficacy evaluable with overall objective response rate (ORR) of 32.6%, confirmed objective response rate (cORR) of 23.3%, and confirmed disease control rate (cDCR) of 81.4%. As the data cutoff date, 4 out of 10 cORR patients had progressed, the median duration of response (mDoR) was 7.0 (4.0-NC) months, and the 6-month DoR rate was 63%."

P1 data • Pancreatic Ductal Adenocarcinoma

Innovent to Present Clinical Data of Multiple Novel Molecules at ESMO Asia 2024 (PRNewswire) - "Innovent Biologics...announces that nearly 10 accepted clinical data of its novel oncology molecules, including an oral presentation of updated Phase 1 result of its novel TOPO1i CLDN18.2 ADC (IBI343) in previously-treated pancreatic cancer, will be released at the European Society of Medical Oncology Asia (ESMO Asia) Congress 2024 from Dec 06-08, 2024, in Singapore."

Clinical data • Cholangiocarcinoma • Colorectal Cancer • Hepatocellular Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Pancreatic Cancer

Anti-claudin18.2 (CLDN18.2) antibody-drug conjugate (ADC) IBI343 in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC): Updated results from a phase I study (ESMO Asia 2024) - P1 | "Results As of July 6, 2024, 43 pts were enrolled from China and Australia (median age: 60.0 years, males: 55.8%, prior treatments ≥2L: 53.5%, prior irinotecan therapy: 46.5%, prior immunotherapy: 22.0%). Conclusions IBI343 was well tolerated and continued to show favorable safety profiles and encouraging efficacy in CLDN18.2-positive PDAC. The trial continues to enroll and more data will be presented at the meeting."

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

Technical, preclinical, and clinical developments of Fc-glycan-specific antibody-drug conjugates. (PubMed, RSC Med Chem) - "Notably, JSKN003 and IBI343 have demonstrated promising results in phase 1 trials and are advancing into phase 3 studies. This review discusses the advantages of Fc-glycan-conjugation, various glycan-specific conjugation techniques, and the preclinical and clinical development of gsADCs. While challenges such as increased manufacturing cost for large-scale production need continuous innovation to overcome and there are different opinions regarding the pros and cons of reduced/diminished affinities to Fc gamma receptors, ongoing research and clinical progress underscore the potential of gsADCs to renovate ADC cancer therapy."

Journal • Preclinical • Review • Oncology

CIBI343A101: A First-in-human Study of IBI343 in Subjects With Locally Advanced Unresectable or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=470 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | N=210 ➔ 470 | Trial completion date: Oct 2024 ➔ Dec 2025 | Trial primary completion date: May 2024 ➔ Dec 2025

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CLDN18

Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review). (PubMed, Int J Mol Med) - "The human/humanized anti‑CLDN18.2 mAb osemitamab, and ADCs AZD0901, IBI343 and LM‑302, with single‑agent ORRs of 28‑60%, have been tested in phase III clinical trials. In addition, bsAbs, CAR T cells and their derivatives targeting CLDN4, 6 or 18.2 are in phase I and/or II clinical trials. AZD0901, IBI343, zolbetuximab and the anti‑CLDN1 mAb ALE.C04 have been granted fast track designation or priority review designation by the US Food and Drug Administration."

Journal • Review • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • CLDN1 • CLDN18 • CLDN4 • CLDN6

Targeting Claudin-18.2 for cancer therapy: updates from 2024 ASCO annual meeting. (PubMed, J Hematol Oncol) - "At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the final results of the phase 3 SPOTLIGHT trial were presented, demonstrating a significant survival benefit from the addition of the CLDN18.2-specific antibody zolbetuximab to chemotherapy in the first-line treatment of advanced gastroesophageal adenocarcinomas with ≥ 75% CLDN18.2 expression...In addition, several early-phase trials presented at ASCO 2024 investigate other CLDN18.2-targeting approaches in CLDN18.2-positive refractory advanced solid tumors, including the CLDN18.2-targeting antibody-drug conjugates LM-302 and IBI343, the bispecific anti-CLDN18.2/CD3 antibody IBI38, and the chimeric antigen receptor T cell therapy satricabtagene autoleucel. These novel approaches could potentially expand the benefit of CLDN18.2-targeting therapies to a broader range of tumor types and to tumors expressing lower levels of CLDN18.2."

Journal • Review • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18