satricabtagene autoleucel (CT041)

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the final results of the phase 3 SPOTLIGHT trial were presented, demonstrating a significant survival benefit from the addition of the CLDN18.2-specific antibody zolbetuximab to chemotherapy in the first-line treatment of advanced gastroesophageal adenocarcinomas with ≥ 75% CLDN18.2 expression...In addition, several early-phase trials presented at ASCO 2024 investigate other CLDN18.2-targeting approaches in CLDN18.2-positive refractory advanced solid tumors, including the CLDN18.2-targeting antibody-drug conjugates LM-302 and IBI343, the bispecific anti-CLDN18.2/CD3 antibody IBI38, and the chimeric antigen receptor T cell therapy satricabtagene autoleucel. These novel approaches could potentially expand the benefit of CLDN18.2-targeting therapies to a broader range of tumor types and to tumors expressing lower levels of CLDN18.2.

Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer. ClinicalTrials.gov identifier: NCT03874897 .

P1, N=20, Recruiting, CARsgen Therapeutics Co., Ltd. | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.

P1, N=134, Completed, Peking University | Recruiting --> Completed

CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy. Clinical Insight: Claudin18.2-targeted CAR T cells can safely provide complete objective and ctDNA response in salvage metastatic GC.

P1/2, N=110, Active, not recruiting, CARsgen Therapeutics Co., Ltd. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2

After a conditioning regimen of fludarabine, cyclophosphamide, and nab-paclitaxel, patients were administered 1-3 cycles of satri-cel... The safety profile and therapeutic efficacy of satri-cel were shown to be promising in heavily pretreated patients with CLDN18.2-positive advanced GC/GEJ and PC. In the Phase 2 study, the first patient with GC received satri-cel in May 2023. Clinical trial information: NCT04404595.

Patients received a pre-conditioning regimen of fludarabine, cyclophosphamide, and 100mg/m2 nab-paclitaxel before CT041 CAR-T infusion...Results A 57-year-old man with metastatic gastric cancer to the liver (HER2 negative, PD-L1 CPS 10%) progressed after 5 cycles of FOLFOX+Nivolumab and 4 cycles of FOLFIRI/Ramucirumab...Again, he had G1 CRS with fever, which was resolved without tocilizumab...Conclusions Repeated dosing of anti-claudin 18. 2 CAR-T cells (CT041) was safe and deepened tumor response was observed after repeated dosing.

Patient experienced grade 2 CRS, which was controlled with tocilizumab...Elevating IL-8 and declining TGF-β1 were also observed. The tumor is still under well control until the last follow-up on July 18, 2023.

P1, N=20, Recruiting, CARsgen Therapeutics Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=20, Not yet recruiting, CARsgen Therapeutics Co., Ltd.

Tumor-informed ctDNA correlates with response to CAR-T cell therapy in gastrointestinal malignancies. Ongoing clinical trials of CT041 CAR-T cell therapy will continue ctDNA analysis prospectively. Characteristics of initially ctDNA positive patients receiving CAR-T therapy.

The results of this study suggested that CLDN18.2-positive tumors had unique clinicopathological features, which provided a theoretical basis for the treatment of CLDN18.2 positive tumors.

P1b/2, N=110, Recruiting, CARsgen Therapeutics Co., Ltd. | Phase classification: P1b --> P1b/2

In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC.

These preliminary results suggest that CT041 had manageable safety/tolerability profile and promising efficacy in patients with previously treated advanced G/GEJ cancer. This study is ongoing with further investigation of CT041 in phase II underway.

All patients completed a conditioning regimen consisting of fludarabine, cyclophosphamide, and nab-paclitaxel prior to CT041 CAR T cells...Only one patient received tocilizumab... These preliminary results indicate that CT041 therapy was safe and had therapeutic efficacy in patients with advanced GI cancers. In heavily pre-treated gastric cancer, CT041 may have significantly improved anti-tumor activity compared to historical treatment regimens.

P1/2, N=192, Recruiting, CARsgen Therapeutics Co., Ltd. | N=102 --> 192 | Trial completion date: Dec 2022 --> Jun 2038 | Trial primary completion date: Sep 2022 --> Jun 2024

P1b, N=108, Recruiting, CARsgen Therapeutics Co., Ltd. | N=30 --> 108 | Trial primary completion date: Jun 2022 --> Jun 2025

P1, N=123, Recruiting, Peking University | N=70 --> 123 | Trial completion date: Mar 2022 --> Mar 2024 | Trial primary completion date: Mar 2022 --> Mar 2021

P1, N=70, Recruiting, Peking University | N=50 --> 70 | Trial primary completion date: Mar 2021 --> Mar 2022

P=N/A, N=18, Active, not recruiting, Kang YU | Recruiting --> Active, not recruiting | N=48 --> 18 | Trial completion date: Dec 2021 --> Dec 2023 | Trial primary completion date: Dec 2019 --> Dec 2020