A Phase 1 Single Arm, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MT027 in Patients with Pleural Malignant Tumors

Brief Summary

Detailed Description

MT027 will be given intrapleural injection via pleural cavity puncture on Day 1 of the first 28-day cycle, followed by a 28-day DLT observation period. After the first cycle, if the subject does not experience any unacceptable toxicities and disease progress, additional treatment may be continued every three weeks thereafter. The second study drug injection of Cycle 2 will occur on one to two days after Day 28, and the subsequent study drug administrations will be on first or second day of each successive 21 day-cycle. After receiving the first ICV administration of the study drug, the subject will be observed in the hospital with accessibility to bedside monitors and emergency care for a minimum of seven consecutive days, and discharged after the safety assessments are performed without safety concerns at the discretion of the PI. The subject will be further assessed for safety evaluation on Day14 and Day 28, prior to the initiation of the second injection . A shortened observation period may begin with the second injection at the discretion of the principal investigator (PI). Subjects on-study will receive treatment until intolerable toxicity based on PI's clinical assessment , disease progression, voluntary withdrawal or death. Dose reduction of MT027 may be considered for optimal safety management of the subject, upon the discussion with the Sponsor Medical Monitor. Study drug may be temperately interrupted to allow safety management at the subject level and will resume the study treatment dose after patient's adverse events are recovered to the grade I level, per PI's discretion. Study drug treatment should be discontinued in the following circumstances: The Investigator considers that the subject will no longer benefit from the treatment; the subject develops intolerable toxicity or disease progression ; the subject withdraws the informed consent; or the subject is lost to follow-up. Subjects who complete the study or withdraw from the study for any reason should be followed at the end of treatment/early termination (EOT/ET) within 30 days from the last study drug infusion or becoming aware of the study discontinuation. A telephone follow-up every 12 weeks post EOT/ET for a maximum of 15 years after the 1st dose will be performed, as deemed clinically necessary. Dose escalation will follow a standard 3+3 design. Three dose levels will be explored. Dose escalation will depend on the proportion and intensity of observed toxicities. The number of CAR-T cells in a given cohort could be revised upon the data review of upcoming safety and PK/PD data during the study. The different dose level(s) could be implemented during the escalation phase, if clinically deemed necessary.

Primary Outcomes