CD5CAR-NK Cells for Refractory Invasive Mold Disease

CD5CAR-NK is a first-in-human, pilot, dose-escalation, and single-site study to evaluate the safety of CD5CAR-CBNK in patients with invasive mold diseases (IMD).

The study population consists of patients aged ≥18 years with refractory mold infections.

The number of patients treated will be 10.

This is a dose-escalation study including 3 cohorts. The dose escalation scheme will follow the following scheme:

Cohort 1(3 patients) The sentinel patient of cohort 1 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at day 0. Intra-patient safety will be reviewed daily following the first dose. The second dose (day+3) and third (day+6) will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).

Cohort 1 is planned to include 3 evaluable patients. If a patient does not receive the full planned dosing schedule (all 3 doses), additional patients will be enrolled until at least 3 patients have completed the full prescribed treatment for this cohort. Escalation to Cohort 2 will only occur once safety data from 3 fully-treated patients have been reviewed.

The first subject in each cohort will be dosed and undergo a safety observation period between administrations. The second subject will be dosed 7 days after the first subject completes treatment and after review of safety data. The third subject will be dosed 3 days after the last dose of the second subject, subject to confirmation of acceptable safety.

Cohort 2 (3 patients) The sentinel patient of cohort 2 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at days 0,3 and 6 followed by 25 x106 CAR+ cells at days 9 and 12. Intra-patient safety will be reviewed daily following the first 25 million dose. The dose at day +12 will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).

Cohort 3 (4 patients) The sentinel patient of cohort 3 will receive 10 x106 CAR+ cells of CD5CAR-CBNK at days 0,3 and 6 followed by 25 x106 CAR+ cells at days 9 and 12, and additionally 50 x106 CAR+ cells at days 15 and 18. In this occasion, intra-patient safety will be reviewed daily following the first 50 million dose. The dose at day +18 will only be administered after a safety review from clinicians that confirms the absence of dose-limiting toxicities (DLTs).

• Evaluate the safety and tolerability of CD5CAR-CBNK cells. [Срок оценки: at 6 and 12 weeks]
• Evaluate the safety and tolerability of CD5CAR-CBNK cells. [Срок оценки: at 6 and 12 weeks]
• Evaluate the safety and tolerability of CD5CAR-CBNK cells. [Срок оценки: During the first year after first administration]
• Evaluate the safety and tolerability of CD5CAR-CBNK cells. [Срок оценки: During the first year after first administration]
• Evaluate the safety and tolerability of CD5CAR-CBNK cells. [Срок оценки: During the first year after first administration]
• Assess the efficacy of CD5CAR-CBNK cells. [Срок оценки: at day 15, day 28, 6 and 12 weeks.]
• Assess the efficacy of CD5CAR-CBNK cells. [Срок оценки: at day 28, 6 and 12 weeks from the first CD5CAR-CBNK cell infusion and from study inclusion.]
• Assess the efficacy of CD5CAR-CBNK cells. [Срок оценки: at day 28, 6 and 12 weeks from the first CD5CAR-CBNK cell infusion and from study inclusion.]
• Assess the efficacy of CD5CAR-CBNK cells. [Срок оценки: at day 28, 6 and 12 weeks from the CD5CAR-CBNK cell infusion and inclusion of the patient.]
• Assess the efficacy of CD5CAR-CBNK cells. [Срок оценки: During the first year after first administration]
• Assess the efficacy of CD5CAR-CBNK cells. [Срок оценки: During the first year after first administration]
• Assess the efficacy of CD5CAR-CBNK cells. [Срок оценки: During the first year after first administration]