IBI343 Receives FDA Fast Track Designation for Advanced/Metastatic PDAC


Key Takeaways

  • IBI343 monotherapy received FDA fast track designation for advanced PDAC after one prior therapy.
  • Phase 1 trial showed a 40% overall response rate in patients with CLDN18.2 expression.
Hui Zhou, PhD

Hui Zhou, PhD

The FDA has granted fast track designation to IBI343 monotherapy for patients with advanced unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) that has relapsed and/or is refractory to 1 prior line of therapy.1

Findings from a phase 1 trial (NCT05458219), which were presented at the 2024 ASCO Annual Meeting, showed that as of January 15, 2024, patients in this population who received the agent at a dose of 6 mg/kg every 3 weeks and had claudin 18.2 (CLDN18.2) expression of 1+, 2+, or 3+ staining intensity by immunohistochemistry (IHC) of at least 60% (n = 10) achieved an overall response rate (ORR) of 40%.1,2 Two of these patients had a confirmed partial response (PR).2

“Pancreatic cancer is highly malignant and difficult to diagnose early,” Hui Zhou, PhD, senior vice president of Innovent Biologics, stated in a news release.1 “At present, the treatment of [patients with] advanced pancreatic cancer is still based on systemic chemotherapy. The clinical options for the second-line treatment are particularly limited, with response rates of only 6% to 16% and median survival periods of only about 3 to 6 months. There are urgent clinical needs to be met. As the world's first CLDN18.2 antibody-drug conjugate [ADC] to obtain fast track designation certification in this difficult-to-treat cancer, IBI343 single-agent therapy shows encouraging efficacy and tolerable safety in the late-line treatment of patients with advanced pancreatic cancer. We will continue to confirm its efficacy and safety in this disease in subsequent clinical trials and also explore IBI343 in combination therapy and other solid tumors, including gastric cancer.”

IBI343 is a recombinant monoclonal ADC directed against CLDN18.2. IBI343 binds to CLDN18.2-expressing tumor cells, resulting in CLDN18.2-dependent ADC internalization. After lysosomal processing of the ADC, its active drug, TOP1i, is released, causing DNA damage and tumor cell apoptosis. TOP1i can also diffuse through the plasma membrane and promote a “bystander killing effect” on neighboring cells.

As of December 19, 2023, the phase 1 trial had enrolled 35 patients with locally advanced unresectable or metastatic PDAC or biliary tract cancer who had progressed on or were intolerant to standard treatment and had at least 1 measurable tumor lesion per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.2 Patients in the dose-expansion cohort were required to have CLDN18.2 expression of 1+, 2+, or 3+ staining intensity by IHC of at least 40%. Patients received IBI343 intravenously at either 6 mg/kg (n = 17) or 8 mg/kg (n = 18) every 3 weeks. The trial’s primary end point was safety. Key secondary end points included ORR, disease control rate, duration of response, and progression-free survival.

The safety profiles of IBI343 in the PDAC and biliary tract cancer cohorts were comparable with the safety outcomes in the overall study population. Treatment-emergent adverse effects (TEAEs) occurred in 91.4% of patients, and the rate of grade 3 or higher TEAEs was 37.1%. Treatment-related AEs (TRAEs) occurred in 80.0% of patients, and grade 3 or higher TRAEs were reported in 25.7% of patients. No TRAEs led to death. The most common TRAEs were anemia (grade 1/2, 37.2%; grade ≥3, 5.7%), decreased neutrophil counts (17.2%; 11.4%), vomiting (25.7%; 0%), nausea (25.7%; 0%), decreased white blood cell counts (20.0%; 2.9%), decreased appetite (17.1%; 0%), fatigue (11.4%; 0%), asthenia (11.4%; 0%), hypoalbuminemia (11.4%; 0%), increased aspartate aminotransferase (8.5%; 2.9%), and increased alanine aminotransferase (11.4%; 0%).

Among 25 efficacy-evaluable patients with PDAC and biliary tract cancer with positive CLDN18.2 expression of at least 40%, 5 patients with PDAC achieved a PR.

Previously, the FDA approved the investigational new drug application for IBI343 for the treatment of patients with PDAC.1 Additionally, in May 2024, the agent received breakthrough therapy designation from China’s National Medical Products Administration for use as monotherapy in patients with CLDN18.2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after 2 prior lines of systemic therapy. The phase 3, multicenter G-HOPE-001 trial (NCT06238843) is planned to further investigate IBI343 in this gastric/GEJ cancer population.


  1. Innovent receives fast track designation from the U.S. FDA for IBI343 (TOPO1i anti-CLDN18.2 ADC) as monotherapy for advanced pancreatic cancer. News release. Innovent. June 13, 2023. Accessed June 13, 2024.
  2. Yu X, Zhang J, Tazbirkova A, et al. Safety and efficacy of IBI343 (anti-claudin18.2 antibody-drug conjugate) in patients with advanced pancreatic ductal adenocarcinoma or biliary tract cancer: preliminary results from a phase 1 study. J Clin Oncol. 2024;42(suppl 16):3037. doi:10.1200/JCO.2024.42.16_suppl.3037
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