Satri-cel Improves PFS in CLDN18.2+ Advanced Gastric/GEJ Cancers

Previous findings showed a manageable safety profile associated with satri-cel.

The investigational autologous CAR T-cell therapy satricabtagene autoleucel (satri-cel; CT041) yielded a statistically significant progression-free survival (PFS) improvement vs physician’s choice of therapy among patients with Claudin 18.2 (CLDN18.2)–positive advanced gastric or gastroesophageal junction (GEJ) cancers following at least 2 prior lines of treatment, according to findings from the phase 2 CT041-ST-01 trial (NCT04581473).¹

Treatment with satri-cel met the trial’s primary end point of PFS per independent review committee (IRC) assessment. The agent significantly improved PFS compared with investigator’s choice of therapy, which included paclitaxel, docetaxel, irinotecan, rivoceranib, or nivolumab (Opdivo).

Previous findings showed a manageable safety profile associated with satri-cel.

“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 on] at least 2 prior lines of therapy,” Zonghai Li, MD, PhD, founder, chairman of the Board, chief executive officer, and chief scientific officer at CARsgen Therapeutics, the developer of satri-cel, stated in the press release.¹ “We anticipate submitting a [new drug application] to the [National Medical Products Administration] in the first half of 2025 and look forward to satri-cel becoming the world’s first CAR T product for solid tumors, bringing hope to more patients as soon as possible. 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.”

Developers designed satri-cel to target solid tumors with positive CLDN18.2 expression, particularly among those with gastric or GEJ cancers and pancreatic cancer. The FDA previously granted regenerative medicine advanced therapy (RMAT) designation to satri-cel as a treatment for patients with advanced CLDN18.2-positive gastric or GEJ cancer in January 2022.² Additionally, the agency conferred orphan drug designation to satri-cel for the same patient population in October 2020.³

In the multicenter CT041-ST-01 trial, patients were assigned to receive satri-cel up to 3 times via autologous CAR T-cell injection infusion or physician’s choice of best supportive care.⁴ The trial included dose-escalation and dose-expansion portions in phase 1b; investigators designed phase 2 to verify the efficacy and safety of satri-cel in gastric or GEJ cancers.

The trial’s primary end points included the incidence of treatment-related adverse effects (TRAEs) and the maximum tolerated dose in phase 1b as well as PFS per IRC assessment in phase 2. Secondary end points included objective response rate, overall survival, duration of response, and disease control rate.

Patients 18 to 75 years old with pathologically diagnosed advanced gastric or GEJ adenocarcinoma following 2 or more prior lines of therapy, tumor tissue samples that tested positive for CLDN18.2 expression, and an estimated life expectancy of more than 12 weeks were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 or 1 at screening and sufficient venous access for mononuclear cell collection.

Those with any uncontrollable infection such as active tuberculosis, active autoimmune diseases such as psoriasis or rheumatoid arthritis, or prior receipt of any gene-modified cell therapies including CAR T-cell therapy were ineligible for enrollment. Patients were also unable to enroll if they had brain metastasis, a high risk of hemorrhage or perforation, requirement of anticoagulant therapy, requirement of continuous anti-platelet therapy, or a history of organ transplantation or anticipation of undergoing this type of treatment.

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 Holdings Limited. December 30, 2024. Accessed January 2, 2025. https://tinyurl.com/yc5s7mfb
2. CARsgen announces CT041 CAR T-cell product candidate granted RMAT designation by the FDA. News release. CARsgen Therapeutics Holdings Limited. January 10, 2022. Accessed January 2, 2025. https://tinyurl.com/5n7938nr
3. CARsgen Therapeutics granted orphan drug designation by the US FDA for CT041 CLDN18.2 CAR-T cells for the treatment of gastric and gastroesophageal junction cancers. News release. CARsgen Therapeutics Holdings Limited. October 5, 2020. Accessed January 2, 2025. https://tinyurl.com/32rfbjwt
4. Study to evaluate the efficacy, safety and pharmacokinetics of CT041 autologous CAR T-cell injection. ClinicalTrials.gov. Updated March 6, 2024. Accessed January 2, 2025. https://tinyurl.com/4fm53s86