Innovent Biologics announced updated Phase 1 study results of IBI343, an innovative anti-CLDN18.2 antibody-drug conjugate (ADC), for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC) at the ESMO Asia Congress 2024. The data highlighted encouraging efficacy and a favorable safety profile in patients with previously treated, CLDN18.2-positive PDAC.
Efficacy Data
The Phase 1/1b multi-regional trial (NCT05458219) evaluated IBI343 in a dose escalation and expansion study. As of September 6, 2024, 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 patients had received at least one prior line of therapy, with 60.5% having received two or more lines.
The efficacy-evaluable patients (n=43) demonstrated:
- Overall objective response rate (ORR) of 32.6%
- Confirmed objective response rate (cORR) of 23.3%
- Confirmed disease control rate (cDCR) of 81.4%
As of the data cutoff, the median duration of response (mDoR) was 7.0 months (4.0-NC), with a 6-month DoR rate of 63%. The median progression-free survival (mPFS) was 5.3 months (4.1-7.4).
Safety Profile
The updated safety results indicated a favorable safety profile for IBI343, characterized by consistently low rates of gastrointestinal toxicity and no new safety signals. Treatment-emergent adverse events (TEAEs) were observed in 97.7% of participants, with the most common being anemia, decreased neutrophil count, decreased appetite, nausea, and decreased white blood cell count. Grade ≥3 TEAEs occurred in 51.2% of participants, with no Grade ≥3 nausea or vomiting reported. No TEAE led to death.
Expert Commentary
Professor Xianjun Yu from Fudan University Cancer Hospital noted the urgent clinical need for effective second-line treatments for advanced pancreatic cancer, highlighting the limited response rates and survival outcomes associated with current chemotherapy options. He expressed hope that the continued development of IBI343 could provide a breakthrough therapy for this difficult-to-treat cancer, citing the encouraging efficacy and manageable safety demonstrated in the updated data.
Future Development
Dr. Hui Zhou, Senior Vice President of Innovent, stated that IBI343 is the first ADC candidate globally to demonstrate encouraging efficacy and a favorable safety profile in advanced pancreatic cancer. The FDA has approved IBI343's IND application and granted Fast Track designation, paving the way for a Phase 1 trial in the United States. Innovent plans to continue advancing IBI343's clinical programs to bring new treatments to patients worldwide.
About IBI343
IBI343 is a recombinant human anti-CLDN18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. It is designed to bind to CLDN18.2-expressing tumor cells, leading to ADC internalization, drug release, DNA damage, and tumor cell apoptosis. The released drug can also diffuse across the plasma membrane to kill neighboring cells, resulting in a "bystander killing effect."
IBI343 has received breakthrough therapy designation (BTD) in China for CLDN18.2–positive gastric or gastroesophageal junction (GEJ) adenocarcinoma and Fast Track Designation by the U.S. FDA for advanced unresectable or metastatic PDAC that has relapsed and/or is refractory to one prior line of therapy.
