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

NCT06748872 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: CD-TCR-0042024-516787-28-002024-516787-28
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

  28 days

• Exp Segment: Adverse Events (Safety)

  Incidence of (S)AEs by type, grade and duration

  12 months

Secondary Outcomes (10)

• Objective response rate (ORR)

  12 months

• Correlation of blood levels and the onset and/or severity of IP-related toxicities

  12 months

• Clinical benefit rate (CBR)

  12 months

• Overall survival (OS)

  15 years

• Assess feasibility of MDG1015 generation in study population

  2 years

Study Arms (1)

Administration of MDG1015

EXPERIMENTAL

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.

Drug: Lymphodepletion; Biological: TCR-T cells (MDG1015)

Interventions

Lymphodepletion DRUG

Cylcophosamide and Fludarabine

Administration of MDG1015

TCR-T cells (MDG1015) BIOLOGICAL

TCR-T cells (MDG1015)

Administration of MDG1015

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult, ≥ 18 years of age and weigh ≥ 40 kg for Dose levels 1-3 and ≥ 50 kg for Dose level 4
• 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
• Subject's must have tested positive for HLA-A\*02:01 genotype by a Sponsor designated central laboratory
• 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
• Subjects diagnosed with an eligible indication must have exhausted treatment options with proven survival benefit
• Subjects must have
• measurable disease
• Life expectancy ≥ 3 months per Investigator's opinion
• \. 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)

You may not qualify if:

• Any uncontrolled medical or psychiatric disorder that would preclude participation as outlined
• HLA-A\*02:02 or HLA-A\*02:03 genotype
• Pregnant or lactating women
• Viral serology:
• Known infection with HIV-1/2, CMV (CMV required only for U.S. sites) or HTLV-1/2,
• Active infection with HBV or HCV
• Positive test for Mycoplasma or Treponema Pallidum
• 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)
• Inadequate venous access for or contraindications to leukapheresis
• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to MDG1015 excipients, LDC agents, rasburicase, methylprednisolone or tocilizumab.
• Untreated CNS metastases or active CNS metastases (progressing or requiring corticosteroids for symptoms control) and leptomeningeal disease
• Unstable/active ulcer, varices, or digestive tract bleeding or recent digestive surgery that may have increased risk of bleeding
• 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:
• non-melanoma skin cancer
• curatively treated localized prostate cancer

Sponsors & Collaborators

• Medigene AG: lead

Study Sites (1)

Fred Hutch Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Sarcoma; Liposarcoma, Myxoid; Sarcoma, Synovial

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Connective Tissue

Study Officials

• David Dr. Zhen, MD

  Fred Hutch Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kirsty Dr. Crame, MD

CONTACT

+49892000330; k.crame@medigene.com

Marianne Seibt, BA

CONTACT

m.seibt@medigene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm, open label, multicenter, phase I study following a Bayesian optimal interval (BOIN) design for dose escalation

Study Record Dates

• First Submitted: December 12, 2024
• First Posted: December 27, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): August 1, 2042
• Last Updated: December 27, 2024

Record last verified: 2024-12

Locations

US (1)