Innovent's IBI343 Gets NMPA Breakthrough Therapy Status for Advanced Pancreatic Cancer

Innovent Biologics, Inc., a prominent biopharmaceutical company, has announced that IBI343, a promising therapeutic for pancreatic ductal adenocarcinoma (PDAC), has been granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA). This designation is specifically for IBI343 as a monotherapy for CLDN18.2-positive advanced PDAC patients who have not responded to at least one previous systemic treatment. The potential of IBI343 as a best-in-class agent targeting CLDN18.2 was key to this recognition.

The BTD was awarded following compelling data from an ongoing Phase 1 study conducted across China, Australia, and the U.S., registered under the clinical trial number NCT05458219. This study showcased the safety, tolerability, and antitumor activity of IBI343 in patients with advanced PDAC. Results were shared at the 2024 ESMO Asia Congress, where findings from a dose-expansion cohort were presented. In this cohort, 43 individuals with CLDN18.2-positive advanced PDAC, characterized by high membranous staining intensity, received IBI343 at a dose of 6 mg/kg every three weeks. All had undergone at least one prior line of therapy, with 60.5% having received two or more prior treatments. The study reported a confirmed overall objective response rate (ORR) of 23.3%, with progression-free survival (PFS) events recorded in 26 patients, leading to a median progression-free survival (mPFS) of 5.3 months.

Earlier, in May 2024, the CDE had already granted IBI343 its first BTD for treating CLDN18.2-positive advanced gastric and gastro-esophageal junction adenocarcinoma (GC) after two prior treatments. Furthermore, the U.S. Food and Drug Administration (FDA) awarded IBI343 Fast Track Designation in June 2024 for treating advanced PDAC that has recurred or is resistant after one prior line of therapy. Subsequently, the first U.S. patient was treated in a Phase 1 study in December 2024.

Dr. Hui Zhou, Senior Vice President of Innovent, highlighted the aggressive nature of pancreatic cancer and the limited options available for second-line treatment. He emphasized the urgent need for improved therapeutic options, noting that IBI343 has demonstrated promising results in late-line treatments for advanced pancreatic cancer. Innovent intends to initiate pivotal multi-regional clinical trials (MRCT) to confirm the efficacy and safety of IBI343 in this context. The company is also exploring its potential in combination therapies for pancreatic cancer and other solid tumors, including gastric cancer.

The NMPA's Breakthrough Therapy Designation is designed to accelerate the development and review process for drugs showing substantial improvement over current treatments for serious diseases, by offering expedited review and enhanced communication with the sponsor.

Pancreatic ductal adenocarcinoma is among the most aggressive cancers, with a five-year survival rate of only about 10%. Despite increasing incidence rates, early detection is rare, posing a significant threat to human health. Current treatments for advanced pancreatic cancer mainly involve systemic chemotherapy, with limited success in second-line treatments. This underscores the critical need for new and effective therapies.

IBI343 is an innovative antibody-drug conjugate (ADC) composed of an anti-CLDN18.2 antibody and the cytotoxic drug exatecan. It works by specifically targeting CLDN18.2-expressing tumor cells, leading to internalization and release of the cytotoxic agent, which induces apoptosis. Additionally, IBI343 has a "bystander killing effect," enabling it to kill neighboring tumor cells. The ADC has shown promising safety and efficacy in Phase 1 studies, and its potential is being investigated in various tumor types, including gastric and pancreatic cancers.