MDG1015 is a third generation TCR-T therapy product targeting NY-ESO-1/LAGE-1a armored and enhanced by the PD1-41BB costimulatory switch protein (CSP). The study purpose is to establish the safety, tolerability and preliminary efficacy of MDG1015 in patients with epithelial ovarian cancer, gastroesophageal adenocarcinoma, round cell liposarcoma and/or synovial sarcoma that expresses NY-ESO-1 and/or LAGE-1a. The main questions this clinical trial aims to answer are: Can this TCR-T therapy MDG1015 be given to patients safely? What is the optimal dose of the TCR-T therapy MDG1015? If and what side effects do participants experience after receiving the TCR-T therapy MDG1015? Do participants experience a potential disease response after receiving the TCR-T therapy MDG1015? Participants will: Receive (in most cases) 1 single infusion of MDG1015 at a pre-defined dose level and will be followed up regularly up to 1 year. After one year, participants will enter the long term follow-up part up to 15 years after being treated. Any side effects and/or potential disease response will be documented during this period.
The clinical study consists of screening, leukapheresis of mononuclear cells, LDC, followed by a single MDG1015 infusion on Day 0 and a subsequent hospitalization period of at least 3 days for in-patient safety monitoring. All Subjects who have received an MDG1015 infusion will continue to be followed regularly for safety and efficacy assessments in a post-treatment follow-up through month 12 (Y1) and long-term follow-up (LTFU) through years 2 - 15 in an out-patient setting. Dose Escalation Segment (DE) will evaluate an anticipated number of 4 dose levels to establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D). During the cohort expansion (CE) segment the MTD/RP2D will be confirmed
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Cylcophosamide and Fludarabine
TCR-T cells (MDG1015)
Fred Hutch Cancer Center
Seattle, Washington, United States
DE Segment: Adverse Events and Dose Limiting Toxicities (Safety and Tolerability)
Incidence and severity of adverse events to establish RP2D measured by dose limiting toxicities (DLTs) up to 28 days post infusion
Time frame: 28 days
Exp Segment: Adverse Events (Safety)
Incidence of (S)AEs by type, grade and duration
Time frame: 12 months
Objective response rate (ORR)
Proportion of Subjects having a confirmed complete response (CR) or partial response (PR) per RECIST v1.1
Time frame: 12 months
Correlation of blood levels and the onset and/or severity of IP-related toxicities
Correlation of certain blood levels in serum over time and any correlation between these levels and the onset and/or severity of IP-related toxicities
Time frame: 12 months
Clinical benefit rate (CBR)
Proportion of Subjects having a sustained confirmed stable disease (SD) or a confirmed PR or CR for any duration of time per RECIST v1.1
Time frame: 12 months
Overall survival (OS)
The interval between MDG1015 infusion and date of death by any cause
Time frame: 15 years
Assess feasibility of MDG1015 generation in study population
Number of MDG1015 products manufactured which comply with the pre-defined release specifications
Time frame: 2 years
Progression Free Survival (PFS)
The interval between MDG1015 infusion and date of disease progression or death per RECIST v1.1
Time frame: 12 months
Duration of response (DOR)
The interval between the first documented response following MDG1015 infusion until first documented disease progression or death
Time frame: 12 months
Best overall response (BOR)
The best response recorded from the start of the treatment until disease progression (taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started)
Time frame: 12 months
Time to response (TTR)
The interval between MDG1015 infusion and first documented CR or PR per RECIST v1.1
Time frame: 12 months
Levels of MDG1015 in blood over time
Time frame: 12 months
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