Satri-Cel Improves PFS in Pretreated CLDN18.2+ Advanced Gastric/GEJ Cancer

Treatment with the Claudin18.2 (CLDN18.2)–directed autologous CAR T-cell therapy satricabtagene autoleucel (satri-cel; CT041) led to a statistically significant improvement in progression-free survival (PFS) compared with physician’s choice of therapy in patients with CLDN18.2-positive advanced gastric/gastroesophageal junction (GEJ) cancer that had progressed following at least 2 prior lines of therapy, according to topline data from the phase 2 CT041-ST-01 trial (NCT04581473).1

Findings showed that the study met its primary end point of PFS per independent review committee assessment. Previous data have shown that the safety profile of satri-cel is manageable, according to an announcement from CARsgen Therapeutics, the developer of the CAR T-cell therapy.

“We are thrilled to see that satri-cel has achieved positive results in the pivotal phase 2 clinical trial in China. The study demonstrates that satri-cel provides significant benefits to [patients with] gastric cancer who have [progressed after] at least 2 prior lines of therapy. This represents a groundbreaking milestone for the field of [CAR T-cell] therapies against solid tumors,” Zonghai Li, MD, PhD, founder, chairman of the board, chief executive officer, and chief scientific officer at CARsgen Therapeutics, stated in a news release. “We anticipate submitting a new drug application to the National Medical Products Administration [in China] in the first half of 2025... Additionally, we will continue to explore the potential of satri-cel in adjuvant therapy for gastric and pancreatic cancers, aiming to deliver even greater benefits to patients.”

In January 2022, the FDA granted regenerative medicine advanced therapy designation to satri-cel for the treatment of patients with advanced gastric/GEJ cancer with CLDN18.2-positive tumors. The CAR T-cell therapy also received orphan drug designation from the FDA for gastric/GEJ cancer in 2020.

CT041-ST-01 was an open-label, multicenter trial conducted in China, where investigators enrolled patients 18 to 75 years of age.2 In phase 1b, patients were required to have pathologically diagnosed advanced gastric/GEJ adenocarcinoma whose disease progressed after least 2 prior lines of treatment; or pathologically diagnosed advanced pancreatic cancer that progressed after at least 1 prior line of therapy. Phase 2 included only patients with pathologically diagnosed advanced gastric/GEJ adenocarcinoma that had progressed after at least 2 prior lines of therapy. In phase 1b, tumor tissue samples needed to be CLDN18.2 positive; in phase 2, samples needed to be CLDN18.2 positive and HER2 negative.

Other key inclusion criteria consisted of a life expectancy of longer than 12 weeks; measurable disease per RECIST 1.1 criteria; and an ECOG performance status of 0 or 1.

Patients were excluded if they had active autoimmune diseases; had any active infection; had previously received any gene-modified cell therapy; had a history of or were awaiting solid organ transplant; or had undergone major surgery or experienced significant trauma within 4 weeks prior to apheresis, or were planning to undergo major surgery during the study.

In phase 2, patients were randomly assigned in a 2:1 fashion to receive satri-cel or investigator’s choice of therapy, which included paclitaxel, docetaxel, irinotecan, apatinib, or nivolumab (Opdivo).1

Along with the primary end point of PFS, secondary end points in phase 2 included overall survival, objective response rate, duration or response, and disease control rate.2

Satri-cel is also being evaluated in patients with advanced solid tumors in the phase 1 CT041-CG4006 trial (NCT03874897) in China; after adjuvant chemotherapy in patients with pancreatic cancer in the phase 1 CT041-ST-05 trial (NCT05911217) in China; and in patients with advanced gastric or pancreatic adenocarcinoma in the phase 1b/2 CT041-ST-02 trial (NCT04404595) in North America.1

References

1. CARsgen announces positive topline results from China GC/GEJ pivotal phase II clinical trial of Claudin18.2 CAR-T (satri-cel). News release. CARsgen Therapeutics. December 30, 2024. Accessed January 3, 2025. https://www.carsgen.com/en/news/20241230/
2. Study to evaluate the efficacy, safety and pharmacokinetics of CT041 autologous CAR T-cell injection. ClinicalTrials.gov. Updated March 6, 2024. Accessed January 3, 2025. https://clinicaltrials.gov/study/NCT04581473