Epithelial Ovarian CancerPhase 1EPITOME-1015-INCT06748872
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
A Phase 1 study testing Lymphodepletion and TCR-T cells (MDG1015) in people with Epithelial Ovarian Cancer and Gastro-esophageal Junction Cancer, run by Medigene AG at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epithelial Ovarian Cancer, Gastro-esophageal Junction Cancer, Soft Tissue Sarcoma (STS)
- What is being tested?
- Lymphodepletion and TCR-T cells (MDG1015)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2025to 1 Aug 2042
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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)
Who cannot join
- 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
Show all 23Show fewer
- 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:
- Positive history of esophageal or gastric resection that the Investigator considers is at increased risk of bleeding or perforation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Marianne Seibt, BA contact
About this study
Official title: 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
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:
Read more
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.
Read the detailed description
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
- Epithelial Ovarian Cancer, Gastro-esophageal Junction Cancer, Soft Tissue Sarcoma (STS), Myxoid Liposarcoma, Synovial Sarcoma
- Being tested
- Lymphodepletion, TCR-T cells (MDG1015)
- 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
- Medical subject headings
- Carcinoma, Ovarian Epithelial, Sarcoma, Liposarcoma, Myxoid, Sarcoma, Synovial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LymphodepletionDrug
Cylcophosamide and Fludarabine
TCR-T cells (MDG1015)Biological
TCR-T cells (MDG1015)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Lymphodepletion; Biological: TCR-T cells (MDG1015) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days
Exp Segment: Adverse Events (Safety)
Incidence of (S)AEs by type, grade and duration
Measured: 12 months
Secondary outcomes (10)
Objective response rate (ORR)
Proportion of Subjects having a confirmed complete response (CR) or partial response (PR) per RECIST v1.1
Measured: 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
Measured: 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
Measured: 12 months
Overall survival (OS)
The interval between MDG1015 infusion and date of death by any cause
Measured: 15 years
Assess feasibility of MDG1015 generation in study population
Number of MDG1015 products manufactured which comply with the pre-defined release specifications
Measured: 2 years
Progression Free Survival (PFS)
The interval between MDG1015 infusion and date of disease progression or death per RECIST v1.1
Measured: 12 months
Duration of response (DOR)
The interval between the first documented response following MDG1015 infusion until first documented disease progression or death
Measured: 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)
Measured: 12 months
Time to response (TTR)
The interval between MDG1015 infusion and first documented CR or PR per RECIST v1.1
Measured: 12 months
Levels of MDG1015 in blood over time
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2024
- Study start1 Jul 2025 (estimated)
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Aug 2042 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epithelial Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, open label, multicenter, phase I study following a Bayesian optimal interval (BOIN) design for dose escalation
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medigene AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Dr. Zhen, MD, Principal investigator, Fred Hutch Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06748872
- Sponsor's protocol ID
- CD-TCR-004
- Other IDs
- 2024-516787-28-00, 2024-516787-28
- Acronym
- EPITOME-1015-I
- Status last verified
- Dec 2024
- First submitted
- 12 Dec 2024
- Last updated
- 27 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06748872
- Acronym / sponsor ID
- EPITOME-1015-I / CD-TCR-004
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Medigene AGIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2025 (estimated)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Aug 2042 (estimated)
- First posted
- 27 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, open label, multicenter, phase I study following a Bayesian optimal interval (BOIN) design for dose escalation
| Arm | Type | Receives |
|---|---|---|
| Administration of MDG1015 | Experimental | Drug: Lymphodepletion, Biological: TCR-T cells (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (23 listed)
- 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:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LymphodepletionCylcophosamide and Fludarabine | Drug | Administration of MDG1015 |
| TCR-T cells (MDG1015)TCR-T cells (MDG1015) | Biological | Administration of MDG1015 |
Primary outcome
DE Segment: Adverse Events and Dose Limiting Toxicities (Safety and Tolerability)
Time frame: 28 days
Incidence and severity of adverse events to establish RP2D measured by dose limiting toxicities (DLTs) up to 28 days post infusion
Exp Segment: Adverse Events (Safety)
Time frame: 12 months
Incidence of (S)AEs by type, grade and duration
10 secondary outcomes
Objective response rate (ORR)
Time frame: 12 months
Correlation of blood levels and the onset and/or severity of IP-related toxicities
Time frame: 12 months
Clinical benefit rate (CBR)
Time frame: 12 months
Overall survival (OS)
Time frame: 15 years
Assess feasibility of MDG1015 generation in study population
Time frame: 2 years
Progression Free Survival (PFS)
Time frame: 12 months
Duration of response (DOR)
Time frame: 12 months
Best overall response (BOR)
Time frame: 12 months
Time to response (TTR)
Time frame: 12 months
Levels of MDG1015 in blood over time
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Individual participant dataSharing planned: Undecided
Related trials for Epithelial Ovarian Cancer
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Recruiting
A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer
Ovarian Carcinoma
RecruitingPhase 2
Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer
Ovarian Cancer, Fallopian Tube Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
RecruitingPhase 3
Torvutatug Samrotecan Plus Bevacizumab as First-line Maintenance in Non-Homologous Recombination Deficiency (Non-HRD) Positive Advanced Epithelial Ovarian Cancer
Epithelial Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marianne Seibt, BA contact
David Dr. Zhen, MD principal investigator
Fred Hutch Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lymphodepletion and TCR-T cells (MDG1015) in people with Epithelial Ovarian Cancer and Gastro-esophageal Junction Cancer, run by Medigene AG at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kirsty Dr. Crame, MD (+49892000330, k.crame@medigene.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DE Segment: Adverse Events and Dose Limiting Toxicities (Safety and Tolerability) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024.