IBI343 Receives Breakthrough Therapy Designation in China for Claudin 18.2+ Advanced Gastric/GEJ Cancer


China's NMPA has granted breakthrough therapy designation to IBI343 for use in select patients with claudin 18.2–positive gastric or GEJ adenocarcinoma.

Gastric cancer | Image Credit: © Rasi -

Gastric/GEJ Cancer | Image Credit:
© Rasi -

The National Medical Products Administration (NMPA) of China has granted breakthrough therapy designation (BTD) to IBI343 for use as a single agent in patients with claudin 18.2–positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who experienced disease progression following 2 prior lines of systemic treatment.1

The decision is supported by findings from a phase 1 study (NCT05458219), which indicated that the monotherapy had antitumor activity and showcased an acceptable safety profile in this patient population. The data will be shared at an upcoming medical meeting later this year, according to a news release issued by Innovent Biologics, Inc., the drug developer.

“[Patients with gastric cancer] tend to progress after second-line systematic therapies with poor prognosis and have only a half year of survival expectancy,” Hui Zhou, PhD, senior vice president at Innovent, stated in a news release. “They are in urgent need of effective third-line treatment options. We are glad to see the NMPA granted BTD for IBI343 monotherapy based on the PoC clinical results in gastric cancer, and we will continue to validate its efficacy and safety in the registrational MRCT trial.”

The antibody-drug conjugate (ADC) comprises an anti–claudin 18.2 antibody and the cytotoxic drug exatecan, the latter of which eliminates cancer cells by hindering DNA synthesis. When IBI343 binds to cancer cells that express claudin 18.2, it leads to claudin 18.2–dependent internalization of the drug. When the cleavable linker degrades, it releases the drug and ultimately results in apoptosis of the cancer cells. Notably, IBI343 is thought to have a bystander-killing effect because once released, it spreads across the plasma membrane and eliminates neighboring cancer cells.

The dose-escalation portion of the multicenter, open-label, first-in-human study enrolled patients with histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors who do not have existing standard therapies or ones that are still effective.2 The dose-expansion portion included patients with pathologically documented locally advanced unresectable or metastatic gastric or GEJ cancer and claudin 18.2 expression. To enroll, patients needed to be at least 18 years of age, have at least 1 measurable lesion by RECIST 1.1 criteria, and have acceptable bone marrow and organ function.

If patients had lung cancer, previously received anticancer therapy within 4 weeks of study drug administration, or if they planned to receive other anticancer agents during the study apart from palliative radiotherapy for symptom relief, they were excluded. Other exclusion criteria included receipt of CYP3A4 and/or CYP1A2 inhibitors within 2 weeks of the study drug, unresolved toxicities from prior anticancer treatments, symptomatic central nervous system metastases, and a history of pneumonia that needed corticosteroids, among others.

In the dose-escalation portion of the study, the agent was administered intravenously at various dose levels after accelerated titration for the first 2 levels. The study leveraged a 3+3 dose-escalation design for the dose levels that followed. In phase 1a of the dose-expansion portion of the research, the agent is being evaluated at levels that are equal to or lower than the maximum tolerated dose; in phase 1b, the agent will be evaluated at the recommended phase 2 dose.

The primary objectives of the study are to evaluate the adverse effects (AEs), treatment-emergent AEs, and serious AEs with the ADC, as well as to evaluate dose-limiting toxicities 21 days following the first dose of the study drug.

Secondary objectives include examining pharmacokinetic parameters such as maximum concentration, area under the curve, clearance rate, half-life, apparent volume of distribution, the incidence and characterization of antidrug antibodies; objective response rate; time to response; duration of response; disease control rate; progression-free survival; and overall survival.

Although not yet recruiting, the registrational, multicenter, randomized, open-label phase 3 G-HOPE-001 study (NCT06238843) will compare the safety and efficacy of single-agent IBI343 with investigator’s choice of irinotecan or paclitaxel in patients with previously treated, claudin 18.2–positive, HER2-negative, locally advanced, unresectable or metastatic gastric or GEJ cancer.3


  1. Innovent receives NMPA breakthrough therapy designation for IBI343 (anti-claudin18.2 ADC) as monotherapy for advanced gastric cancer. News release. Innovent Biologics, Inc. May 7, 2024. Accessed May 8, 2024.
  2. A first-in-human study of IBI343 in subjects with locally advanced unresectable or metastatic solid tumors. Updated July 14, 2022. Accessed May 8, 2024.
  3. 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 (G-HOPE-001). Updated February 2, 2024. Accessed May 8, 2024.
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