EPITOME-1015-I: a Study to Investigate the Safety and Tolerability of MDG1015 in Patients with Epithelial Ovarian Cancer, Gastroesophageal Adenocarcinoma, Round Cell Liposarcoma And/or Synovial Sarcoma

NCT ID: NCT06748872

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-01

Study Completion Date

2042-08-01

Brief Summary

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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.

Detailed Description

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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

Conditions

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Epithelial Ovarian Cancer Gastro-esophageal Junction Cancer Soft Tissue Sarcoma (STS) Myxoid Liposarcoma Synovial Sarcoma

Keywords

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TCR-T Therapy dose escalation Third Generation TCR-T Therapy autologous, patient derived CD8+ T cells single arm open label phase I BOIN design NY-ESO-1 LAGE-1a solid tumors PD1-41BB Costimulatory Switch Protein Armoring Enhancement First-in-human

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single arm, open label, multicenter, phase I study following a Bayesian optimal interval (BOIN) design for dose escalation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Administration of MDG1015

MDG1015 is a first-in-class, 3rd generation TCR-T therapy consisting of autologous, patient-derived CD8+ T cells that are transduced with a New York esophageal squamous cell carcinoma-1 (NY-ESO-1)/ L antigen family member-1a (LAGE-1a)-specific, human leukocyte antigen (HLA)-A\*02:01-restricted T cell receptor (TCR) and the costimulatory switch protein (CSP) programmed cell death protein 1 (PD1)-41BB administered following lymphodepletion chemotherapy.

Group Type EXPERIMENTAL

Lymphodepletion

Intervention Type DRUG

Cylcophosamide and Fludarabine

TCR-T cells (MDG1015)

Intervention Type BIOLOGICAL

TCR-T cells (MDG1015)

Interventions

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Lymphodepletion

Cylcophosamide and Fludarabine

Intervention Type DRUG

TCR-T cells (MDG1015)

TCR-T cells (MDG1015)

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Adult, ≥ 18 years of age and weigh ≥ 40 kg for Dose levels 1-3 and ≥ 50 kg for Dose level 4
2. Subject must have a confirmed diagnosis of either High grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer Gastric or esophageal (junction) adenocarcinoma Myxoid (round cell) liposarcoma Synovial sarcoma
3. Subject's must have tested positive for HLA-A\*02:01 genotype by a Sponsor designated central laboratory
4. Subject's tumor must have tested positive for NY-ESO-1 and/or LAGE-1a mRNA expression by a Sponsor designated central laboratory Both ≤1 year old archival tissue or fresh biopsy are allowed
5. Subjects diagnosed with an eligible indication must have exhausted treatment options with proven survival benefit
6. Subjects must have

1. measurable disease
2. Life expectancy ≥ 3 months per Investigator's opinion

8\. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 9. Adequate vital organ function 10. Adequate bone marrow function 11. Adequate coagulation profile 12. Toxicities from prior/ongoing therapies must have recovered to ≤ Grade 2 according to the CTCAE v5.0 or Subject's baseline excluding alopecia 14. Prior toxicities related to surgical procedures should have recovered to Grade ≤ 1 15. Women of childbearing potential (WCBP) or men who can father children must be willing and able to use adequate (e.g. barrier or licensed hormonal methods)

Exclusion Criteria

1. Any uncontrolled medical or psychiatric disorder that would preclude participation as outlined
2. HLA-A\*02:02 or HLA-A\*02:03 genotype
3. Pregnant or lactating women
4. Viral serology:

1. Known infection with HIV-1/2, CMV (CMV required only for U.S. sites) or HTLV-1/2,
2. Active infection with HBV or HCV
3. Positive test for Mycoplasma or Treponema Pallidum
5. Uncontrolled infection(s) requiring intravenous anti-bacterial, anti-viral or anti-fungal treatment within 14 days prior to the first dose of LDC (patients receiving prophylactic antibiotics are eligible)
6. Inadequate venous access for or contraindications to leukapheresis
7. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to MDG1015 excipients, LDC agents, rasburicase, methylprednisolone or tocilizumab.
8. Untreated CNS metastases or active CNS metastases (progressing or requiring corticosteroids for symptoms control) and leptomeningeal disease
9. Unstable/active ulcer, varices, or digestive tract bleeding or recent digestive surgery that may have increased risk of bleeding
10. History of another primary malignancy that requires intervention beyond surveillance or that has not been in remission for at least 1 year. The following are exempt from the 1-year limit:

1. non-melanoma skin cancer
2. curatively treated localized prostate cancer
3. carcinoma in situ (e.g. cervix, bladder, breast)
11. NYHA Class ≥ II, heart failure, unstable angina, a history of recent (≤ 6 months) arrythmias, myocardial infarction or sustained (\> 30 seconds) ventricular tachyarrhythmias
12. Subjects who are dependent on dialysis
13. Subjects with a history of pulmonary embolism or deep vein thrombosis that cannot safely withhold anti-coagulant therapy from leukapheresis until 7 days after administration of MDG1015 as determined by the Investigator
14. Active autoimmune disease requiring systemic therapy except for adequately controlled Type 1 diabetes mellitus, autoimmune hypothyroidism or Grave's disease
15. Previous allogeneic hematopoietic stem cell transplant within the last 5 years or solid organ transplant

Specific to GAC/GEJ Subjects:
16. Positive history of esophageal or gastric resection that the Investigator considers is at increased risk of bleeding or perforation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medigene AG

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Dr. Zhen, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch Cancer Center

Locations

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Fred Hutch Cancer Center

Seattle, Washington, United States

Site Status

Countries

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United States

Central Contacts

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Kirsty Dr. Crame, MD

Role: CONTACT

Phone: +49892000330

Email: [email protected]

Marianne Seibt, BA

Role: CONTACT

Email: [email protected]

Other Identifiers

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2024-516787-28-00

Identifier Type: CTIS

Identifier Source: secondary_id

2024-516787-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CD-TCR-004

Identifier Type: -

Identifier Source: org_study_id