Набор скоро начнётся NCT06748872

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

Фаза I С лечением Epithelial Ovarian Cancer Gastro-esophageal Junction Cancer Soft Tissue Sarcoma (STS) Myxoid Liposarcoma

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: Lymphodepletion, TCR-T cells (MDG1015).
Кому может быть актуально: Состояния в реестре: Epithelial Ovarian Cancer, Gastro-esophageal Junction Cancer, Soft Tissue Sarcoma (STS), Myxoid Liposarcoma. Базовые параметры: от 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: США
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

EPITOME-1015-I: a Phase I Study to Investigate the Safety, Tolerability and Preliminary Efficacy of a Third Generation TCR-T Therapy, MDG1015, in Epithelial Ovarian Carcinoma, Gastroesophageal (Junction) Adenocarcinoma, Myxoid (Round Cell) Liposarcoma And/or Synovial Sarcoma Subjects with Advanced Disease Expressing NY-ESO-1 And/or LAGE-1a

Обзор

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.

Подробное описание

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

Вмешательства

Препарат Lymphodepletion
Cylcophosamide and Fludarabine
Биопрепарат TCR-T cells (MDG1015)
TCR-T cells (MDG1015)

Первичные конечные точки

DE Segment: Adverse Events and Dose Limiting Toxicities (Safety and Tolerability) [Срок оценки: 28 days]
Exp Segment: Adverse Events (Safety) [Срок оценки: 12 months]

Вторичные конечные точки (10)

Objective response rate (ORR) [Срок оценки: 12 months]
Correlation of blood levels and the onset and/or severity of IP-related toxicities [Срок оценки: 12 months]
Clinical benefit rate (CBR) [Срок оценки: 12 months]
Overall survival (OS) [Срок оценки: 15 years]
Assess feasibility of MDG1015 generation in study population [Срок оценки: 2 years]
Progression Free Survival (PFS) [Срок оценки: 12 months]
Duration of response (DOR) [Срок оценки: 12 months]
Best overall response (BOR) [Срок оценки: 12 months]
Time to response (TTR) [Срок оценки: 12 months]
Levels of MDG1015 in blood over time [Срок оценки: 12 months]

Критерии участия

Критерии включения

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

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)

Критерии исключения

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
carcinoma in situ (e.g. cervix, bladder, breast)
NYHA Class ≥ II, heart failure, unstable angina, a history of recent (≤ 6 months) arrythmias, myocardial infarction or sustained (> 30 seconds) ventricular tachyarrhythmias
Subjects who are dependent on dialysis
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
Active autoimmune disease requiring systemic therapy except for adequately controlled Type 1 diabetes mellitus, autoimmune hypothyroidism or Grave's disease
Previous allogeneic hematopoietic stem cell transplant within the last 5 years or solid organ transplant

Specific to GAC/GEJ Subjects: