Editor's note: The 2024 American Society of Oncology (ASCO) Annual Meeting will be held in Chicago, USA from May 31 ~ June 4, 2024 local time. As part of the Education Session at the ASCO Annual Meeting, the much-talked-about ASCO Plenary Series: Rapid Abstract Updates was held on June 1 local time.
A total of 6 abstracts were updated in this event, among which Professor Xu Ruihua from the Cancer Center of Sun Yat-sen University shared the updated results of the phase I study of Claudin18.2 ADC drug CMG901 (AZD0901) in the treatment of patients with advanced gastric cancer/gastroesophageal junction adenocarcinoma, which further clarified the efficacy and safety of CMG901 (AZD0901) in advanced gastric cancer with Claudin18.2 expression, which is expected to bring new options for the treatment of advanced gastric cancer.
According to the 2022 Global Cancer Burden Statistics, gastric cancer is the fifth most common cancer in the world, with 970,000 new cases, and more than one-third of the patients are from China, which seriously threatens the lives and health of the people. For patients with advanced gastric cancer, treatment options that can prolong survival are extremely limited, especially for patients who have failed previous treatments, and their prognosis is generally poor, and the median overall survival (OS) is even less than 10 months, so it is urgent to explore new effective treatment options.
Claudin18.2 is a tight junction protein expressed only in the normal gastric mucosa to maintain normal cell function. Normally, Claudin18.2 is usually buried in tight junctions, but during tumor malignancy, the polarity of gastric mucosal cells changes, resulting in a wide distribution of Claudin18.2 on the surface of the cell membrane, making it easier to access therapeutic antibodies. Previous studies have confirmed that Claudin18.2 can be used as an effective therapeutic target for gastric cancer.
CMG901(AZD0901) is a potential first-in-class Claudin18.2-targeting ADC drug consisting of a humanized Claudin18.2 antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable linker.
At the November 2023 ASCO Plenary Series, the results of this multi-center Phase I clinical study led by Prof. Ruihua Xu's team demonstrated encouraging efficacy and favorable safety data of CMG901 in the treatment of patients with advanced gastric cancer with high expression of Claudin 18.2. The latest efficacy and safety data from the study were presented at the ASCO Annual Meeting.
Study design
This is an open-label, dose-finding and dose-expanding Phase I clinical study to evaluate the safety and tolerability, pharmacokinetic profile, immunogenicity and preliminary efficacy of CMG901 in subjects with advanced solid tumors who have failed standard therapy or have no standard therapy. The primary endpoints in the dose escalation phase are adverse events and dose-limiting toxicities. The primary endpoints in the dose expansion phase are objective response rate (ORR) and the recommended dose for Phase II clinical trials (RP2D).
CMG901 has demonstrated excellent efficacy and good safety and tolerability in the treatment of patients with advanced anti-Claudin 18.2 high-expression gastric cancer/gastroesophageal junction adenocarcinoma. This study provides support for the development of follow-up studies, suggesting that CMG901 is expected to be a new treatment option for patients with Claudin 18.2 high expression gastric cancer in the future.
CMG901 (AZD0901) has been granted IND designation, orphan drug designation and fast track designation by the FDA (Food and Drug Administration) in April 2022. In September 2022, it has also been granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (CNPA) in China. Currently, an international, multicenter phase III study (CTR20240730, NCT06346392) is being conducted to compare the efficacy and safety of CMG901 (AZD0901) monotherapy with investigator's choice of second-line or higher treatment in patients with advanced gastric cancer with CLDN18.2 expression, with clinical locations covering the United States, the United Kingdom, France, Germany, etc.
In the 2024 ASCO General Assembly Series, Professor Xu Ruihua gave a comprehensive and in-depth explanation of the latest results of the Phase I study of CMG901(AZD0901). This research achievement not only lays a solid foundation for the further clinical development of CMG901 (AZD0901) in the field of gastric cancer worldwide, but also plays an important role in promoting the development of the global field of gastric cancer treatment. At the same time, Professor Xu Ruihua conducted extensive and in-depth academic discussions and exchanges with his international counterparts, fully demonstrating the outstanding academic demeanor of mainland scholars and once again making a loud "voice of China" on the international stage. We expect that with the continuous advancement and deepening of related research, CMG901 (AZD0901) can eventually bring therapeutic benefits to patients with solid tumors around the world and contribute to the cause of global health."
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