China Approves World's First CAR-T Therapy for Solid Tumors to Treat Advanced Gastric Cancer

China's NMPA has approved CARsgen Therapeutics' satricabtagene autoleucel (satri-cel, Kaileimei), marking the world's first CAR-T therapy approved for solid tumors. Indicated for advanced, CLDN18.2-positive, HER2-negative gastric cancer, the therapy significantly improved median progression-free survival to 3.25 months compared to 1.77 months for standard treatments. Priced at 990,000 yuan ($146,491) per infusion, satri-cel presents high efficacy alongside notable toxicities, including a 95% incidence of cytokine release syndrome.

Satri-cel NMPA approval

• ▪Satricabtagene autoleucel is approved for Claudin18.2-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma after progressing on at least two prior therapies
• ▪CARsgen Therapeutics priced satricabtagene autoleucel, marketed as Kailimei or Kaileimei, at 990,000 yuan ($146,491) per infusion
• ▪China's National Medical Products Administration approved satricabtagene autoleucel, marking the world's first CAR T-cell therapy approved for solid tumors

CLDN18.2-targeted CAR-T mechanism

• ▪The modified CAR construct of satricabtagene autoleucel includes a CD8α hinge, a CD28 transmembrane region, a CD28 intracellular signaling domain, and a CD3ζ intracellular signaling region
• ▪Satricabtagene autoleucel is an autologous CAR T-cell therapy targeting Claudin18.2 with a modified CAR construct containing a humanized single-chain monoclonal antibody fragment

Phase 2 trial design

• ▪The physician's choice treatment arm in the phase 2 trial consisted of paclitaxel, irinotecan, apatinib, or an anti-PD-1 antibody, alongside best supportive care
• ▪The pivotal phase 2 trial randomized patients to receive either satricabtagene autoleucel at doses up to 250 x 10^6 cells or physician's choice of treatment

Progression-free survival efficacy

• ▪Satricabtagene autoleucel generated a median progression-free survival of 3.25 months compared with 1.77 months for the physician's choice group
• ▪The hazard ratio for progression-free survival between the satricabtagene autoleucel and physician's choice groups was 0.37, demonstrating a statistically significant benefit

Treatment-related adverse events

• ▪The most common grade 3 or higher treatment-related adverse effects for satricabtagene autoleucel were decreased lymphocyte count, decreased white blood cell count, and decreased neutrophil count
• ▪Grade 3 or higher treatment-emergent adverse effects occurred in 99% of evaluable patients in the satricabtagene autoleucel group compared to 63% in the physician's choice group

Cytokine release syndrome incidence

• ▪Cytokine release syndrome was experienced by 95% of patients treated with satricabtagene autoleucel in the phase 2 trial
• ▪Safety served as the primary endpoint in the phase 1b portion of the clinical trial evaluating satricabtagene autoleucel