FLOT + toripalimab

FLOT + toripalimab is a combination therapy that has shown promising results in treating gastric and gastroesophageal junction (GEJ) adenocarcinoma. This combination consists of the standard FLOT chemotherapy regimen (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil) plus toripalimab, which is a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1). ## Efficacy and Clinical Trials In a phase II study of perioperative treatment for resectable gastric/GEJ adenocarcinoma, FLOT + toripalimab demonstrated impressive results with a pathological complete response (pCR) rate of 25.0% and a major pathological response (MPR) rate of 42.9% among patients receiving complete resection[1][3]. This combination therapy showed a well-tolerated safety profile while maintaining promising efficacy[1]. The standard FLOT regimen consists of docetaxel (50 mg/m²), oxaliplatin (85 mg/m²), leucovorin (200 mg/m²), and 5-FU (2600 mg/m²), administered every 2 weeks. When combined with toripalimab (240mg, every 2 weeks), this regimen is typically given as 4 pre-operative and 4 post-operative cycles[1]. ## Mechanism of Action The combination leverages multiple mechanisms to target cancer cells: 1. **FLOT components**: The chemotherapy drugs in FLOT induce immunogenic cell death, increase tumor antigenicity, eliminate immunosuppressive cells, and enhance effector cell function[5]. 2. **Toripalimab**: As a PD-1 inhibitor, toripalimab blocks the interaction between PD-1 and its ligands, preventing the suppression of T-cell activation and enhancing anti-tumor immune responses[3]. The synergistic effect between chemotherapy and immunotherapy appears to be a key factor in the improved efficacy of this combination compared to either approach alone[5]. ## Safety Profile Despite the complex pharmaceutical combinations employed in this therapy, studies indicate that it does not significantly increase toxicity concerns for patients compared to monotherapy approaches[2][5]. The combination maintains a safety profile similar to the individual components while enhancing efficacy[2]. ## Development Status While FLOT + toripalimab has shown promising results in gastric and GEJ adenocarcinoma, research is ongoing to further optimize this immunotherapy regimen. Additional investigation is needed to determine the optimal timing, sequencing, and potential therapeutic windows for this combination therapy[2]. The combination is also being explored in other cancer types, with varying protocols and results. For example, a study in esophageal squamous cell carcinoma (ESCC) using toripalimab with chemoradiotherapy did not show significant benefits compared to standard treatment[4].

Brand names

Loqtorzi

Other names

toripalimab-tpziToripalimab combined with FLOT regimen