On January 8th, 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. Data from the study’s dose-expansion cohort were presented orally at the 2024 ESMO Asia Congress:
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%. 26 patients occurred PFS events, with a median progression-free survival (mPFS) of 5.3 (4.1-7.4) months, and OS data is not yet mature.
The updated safety results demonstrated the favorable safety profile of IBI343 with a consistently low rate of gastrointestinal toxicity and no new safety signals. 97.7% of the participants experienced treatment-emergent adverse events (TEAEs), with the most common TEAEs being anemia, neutrophil count decreased, decreased appetite, nausea, and white blood cell count decreased. 51.2% of the participants experienced ≥ grade 3 TEAEs, and no ≥ grade 3 nausea and vomiting occurred. No TEAE led to death.
About IBI343（Anti-CLDN18.2 ADC）
IBI343 is a recombinant human anti-CLDN18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the CLDN18.2-expressing tumor cells, the CLDN18.2 dependent ADC internalization will occur and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in “bystander killing effect”.
As an innovative TOPO1i ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in Phase 1 clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric and pancreatic cancer.
In May 2024, China’s National Medical Products Administration (NMPA) granted breakthrough therapy designation (BTD) to IBI343 for use as a single agent in patients with CLDN18.2–positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who experienced disease progression following two prior lines of systemic treatment. The Phase 3 trial (NCT06238843) of IBI343 for this indication is ongoing.
In June 2024, IBI343 received Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of advanced unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) that has relapsed and/or is refractory to one prior line of therapy. The multi-regional Phase 1 trial (NCT05458219) of IBI343 for previously treated PDAC is ongoing.
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
Phone Number：4008803716
Email：myimmnet@163.com
References
1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
2.https://cn.innoventbio.com/#/
Post time: Jan-17-2025