NCT05137275

Study of Anti-5T4 CAR-raNK Cell Therapy in Locally Advanced or Metastatic Solid Tumors

Dose Escalation and Extension Study to Evaluate the Safety, Tolerability, and Initial Efficacy of Anti-5T4 CAR-raNK Cell Therapy in Locally Advanced or Metastatic Solid Tumors

• Status: Unknown
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 56 (estimated)
• Sponsor: Shanghai East Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This study is a multicenter, open-label, investigator-initiated trial (IIT), divided into dose escalation (Part A) and dose extension (Part B) phases to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacokinetics (PD) and initial efficacy of conjugated antibody redirecting ready-to-use allogeneic NK (CAR-raNK) cells that target trophoblast glycoprotein (5T4) in patients with locally advanced or metastatic solid tumors.

Detailed description

Part A is a dose escalation study to evaluate maximum toxic dose (MTD) and/or recommended phase II dose (RP2D) which adopts the 3+3 dose escalation design protocol. The dose is respectively 3.0×10\^9 live cells, 6.0×10\^9 live cells and 9.0×10\^9 live cells (if the safety of dose group with 9.0×10\^9 live cells is still good, the Safety Monitoring Committee (SMC) will co-decide whether to continue the dose escalation and the specific dose based on the obtained data on safety, efficacy, and PK). The 3.0×10\^9 live cell dose group is given on days 1 and 3 of each cycle (21 days), and the follow-up dose group is given on days 1 and 8 of each cycle (21 days).3-6 subjects will be enrolled at every dose level. The first and second subjects in the same group shall be enrolled at an interval of at least 7 days, for the purpose of ensuring their safety. Only when the dose-limiting toxicity (DLT) of all subjects in the previous dose group was observed can the enrollment of the next dose group get started. Part B is the dose extension study. After recommended phase II dose (RP2D) is determined in Part A, the SMC will discuss whether to conduct the Part B study. This stage will be carried out in different tumor types with high expression of 5T4 antigen, and 6 to 10 subjects will be enrolled in each tumor type, and all subjects will receive anti-5T4 CAR-raNK cell therapy at RP2D level. Every 21 days is one cycle, and the administration is performed on day 1 and day 8 of each cycle.

Conditions

• Locally Advanced or Metastatic Solid Tumors

Interventions

Type	Name	Description
BIOLOGICAL	Anti-5T4 CAR-raNK Cells	In the 3+3 dose escalation study, the minimum initial dose is 3.0×10\^9 cells and then escalate to 6.0× 10\^9 and 9.0× 10\^9 cells. Every 21 days is one cycle, and intravenous infusion is performed on day 1 and day 3\\8 of each cycle. In dose extension study, the initial dose will be determined by RP2D determined by the results of dose escalation study, and the other intervention methods are consistent.

Timeline

• Start date: 2021-11-24
• Primary completion: 2023-04-01
• Completion: 2023-05-01
• First posted: 2021-11-30
• Last updated: 2022-10-27

Locations

1 site across 1 country: China