CARsgen Therapeutics’ CT041 Shows Promise in Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

In patients with previously treated advanced gastric/gastroesophageal junction adenocarcinoma, chimeric antigen receptor-modified autologous T cells targeting Claudin18.2 (CLDN18.2) (CT041, CARsgen Therapeutics) had a manageable safety/tolerability profile and promising efficacy, according to preliminary data from an ongoing phase 1b/2 study (NCT04581473).¹

The data were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, which is taking place from June 3-7 in Chicago, by Changsong QI, MD, PhyD, of Peking University Cancer Hospital & Institute in China.

The investigators explained that CLDN18.2 is a promising therapeutic target that is often expressed in gastric/gastroesophageal junction cancer. CT041 autologous CAR T-cell injection has shown promising anti-tumor activity in preclinical studies, while results from phase 1 trial suggested that CT041 was well tolerated and had encouraging efficacy in previously treated patients with CLDN18.2-positive advanced gastric/gastroesophageal junction adenocarcinoma. Data from a companion US-based study (NCT04404595) elicited either a response or stable disease in a majority of heavily pretreated patients with CLDN18.2-positive advanced gastric and pancreatic adenocarcinoma, results of which were also presented at ASCO 2022.

In this open-label, multicenter, phase 1b/2 trial, the researchers assessed the safety, tolerability, and efficacy of CT041 in 14 patients with previously treated CLDN18.2-positive advanced gastric/gastroesophageal junction adenocarcinoma. There are 2 stages in the ongoing study. The phase 1b stage is a dose escalation and dose expansion study and the phase 2 stage is to verify the efficacy and safety of CT041 treatment.

From November 2020 to May 2021, a total of 14 patients (medium age 44.5) with gastric/gastroesophageal junction adenocarcinoma cancer were enrolled in phase 1b. Of the patients, 85.7% had received 2 prior lines of treatment and 14.3% had at least 3 lines. Meanwhile, 57.1% had at least 3 metastatic organs, 92.9% had peritoneal dissemination, and 64.3% had signet ring cell carcinoma. For up to 3 doses of the autologous CAR T-cell injection infusion, 3 of the patients received 3.75 × 10⁸ dose level and 11 received 2.5 × 10⁸ dose level, respectively.

The most reported adverse events of grade 3 or higher were hematologic toxicity related with lymphodepletion. No dose-limiting toxicities, treatment-related death, neurologic toxicity, or gastrointestinal toxicities were observed. Most occurrences of cytokine release syndrome (CRS) were grade 1 or 2, and 1 patient experienced grade 4 CRS and fully recovered.

Of the patients, 57.1% achieved partial response, 14.3% showed stable disease. With a median follow-up of 8.9 months (95% CI 5.91, NE), the median progression-free survival (PFS) was 5.6 months (95% CI 1.9, 7.4), and median overall survival was 10.8 months (95% CI 5.1, NE). Seven patients were still alive at last follow-up.

This study is ongoing with further investigation of CT041 in phase 2 underway. CARsgen Therapeutics announced in March that the Center for Drug Evaluation of the National Medical Products Administration of China approved the initiation of the CT041 confirmatory phase 2 study.²

“The treatment options for gastric cancer patients who have failed at least 2 prior lines are very limited. The median progression-free survival of available therapies, including anti-PD-1 monoclonal antibody, is merely about 2 months, indicating an urgent unmet medical need for more innovative and effective drugs,” said Lin Shen, MD, of Beijing Institute for Cancer Research, the principal investigator. In this early study of CT041 led by our center, themedium “PFS of CT041 was over 5 months, which is very promising data.”

REFERENCE

1. QI C, Liu C, Gong J, et al.Safety, tolerability, and preliminary efficacy results in patients with advanced gastric/gastroesophageal junction adenocarcinoma from a phase Ib/II study of CLDN18.2 CAR T-cell therapy (CT041). Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #4017

2. Claudin18.2 CAR T Cells (CT041) Receives Approval to Initiate A Confirmatory Phase II Clinical Trial for advanced GC/GEJ in China. News release. CARsgen Therapeutics, March 3,2022. https://www.prnewswire.com/news-releases/claudin18-2-car-t-cells-ct041-receives-approval-to-initiate-a-confirmatory-phase-ii-clinical-trial-for-advanced-gcgej-in-china-301494828.html