MDG1015 for Ovarian Cancer

(EPITOME-1015-I Trial)

Overseen By Kirsty Dr. Crame, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medigene AG

Must not be taking: Corticosteroids, Anticoagulants

Disqualifiers: Uncontrolled disorders, HIV, HBV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called MDG1015 for certain cancers, such as ovarian cancer, that have specific protein markers (NY-ESO-1 or LAGE-1a). The main goals are to determine the treatment's safety, identify potential side effects, and assess its effectiveness against cancer. Participants will receive one dose of MDG1015 and undergo monitoring for up to 15 years. This trial may suit individuals with eligible cancers who have not responded to other treatments and have a positive test for specific proteins in their tumors. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have a history of pulmonary embolism or deep vein thrombosis, you must be able to safely stop anti-coagulant therapy for a period around the treatment.

Is there any evidence suggesting that MDG1015 is likely to be safe for humans?

Research shows that MDG1015, a new type of T cell therapy, is being tested for safety in treating certain cancers, such as ovarian cancer. In lab studies, MDG1015 has demonstrated strong and lasting effects against tumors, suggesting it might effectively attack cancer cells. However, these lab studies do not involve human subjects.

Specific information on how MDG1015 affects humans is not yet available, as this trial is in its early stages. Early trials typically focus on assessing safety and identifying any side effects. Participants in this trial will receive one dose of MDG1015 and will be monitored for up to 15 years to track side effects and observe the treatment's impact on their cancer. This extended follow-up is standard to ensure the treatment remains safe over time. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

MDG1015 is unique because it represents a cutting-edge approach to treating ovarian cancer using TCR-T cell therapy. Unlike traditional chemotherapy or targeted therapies, MDG1015 uses a patient's own CD8+ T cells, which are genetically modified to specifically target cancer cells expressing the NY-ESO-1 and LAGE-1a antigens. This tailored approach not only aims to enhance the precision and effectiveness of the treatment but also incorporates a costimulatory switch protein to boost the immune response against the cancer. Researchers are excited about this treatment because it offers a personalized and potentially more powerful way to combat ovarian cancer, which could lead to better outcomes for patients.

What evidence suggests that MDG1015 might be an effective treatment for ovarian cancer?

Research shows that MDG1015, the investigational treatment studied in this trial, holds promise for treating cancers such as ovarian cancer. Early laboratory studies have demonstrated that MDG1015 can effectively combat tumors over an extended period. This treatment targets specific proteins in certain cancer cells, aiding the immune system in attacking them. It also includes a special feature that may enhance its effectiveness. Although further research is necessary to confirm these results in humans, early findings are encouraging. ^{1 2 6 7 8}

Who Is on the Research Team?

David Dr. Zhen, MD

Principal Investigator

Fred Hutch Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with specific cancers (epithelial ovarian, gastroesophageal adenocarcinoma, round cell liposarcoma, synovial sarcoma) that express NY-ESO-1/LAGE-1a. Participants must be able to receive a single infusion of the study drug and commit to long-term follow-up.

Inclusion Criteria

I am fully active or can carry out light work.

My vital organs are functioning well.

My bone marrow is working well.

Exclusion Criteria

I have untreated or active brain metastases or leptomeningeal disease.

I cannot stop my blood thinner safely for a week after a specific treatment, as decided by my doctor.

I have an autoimmune disease but it's not Type 1 diabetes, hypothyroidism, or Grave's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and LDC

Leukapheresis of mononuclear cells and lymphodepletion chemotherapy (LDC) prior to MDG1015 infusion

1-2 weeks

Treatment

Participants receive a single infusion of MDG1015 followed by at least 3 days of in-patient safety monitoring

1 week

1 visit (in-patient)

Post-treatment Follow-up

Participants are monitored regularly for safety and efficacy assessments

12 months

Regular visits (out-patient)

Long-term Follow-up

Participants enter long-term follow-up for safety and survival assessments

15 years

What Are the Treatments Tested in This Trial?

Interventions

• MDG1015

Trial Overview The trial tests MDG1015, a TCR-T therapy targeting certain cancer antigens with an added costimulatory switch protein. It aims to determine safety, optimal dosage, side effects, and potential disease response after treatment.

How Is the Trial Designed?

Group I: Administration of MDG1015 Experimental Treatment 2 Interventions

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 Is Running the Clinical Trial?

Medigene AG

Lead Sponsor

Trials

5

Recruited

130+

Citations

1. medigene.com medigene.com/science/pipeline/mdg1015/

MDG1015 - Medigene AG This data highlighting the enhancement of the TCR-T therapy through the CSP shows MDG1015's potential to lead to improved clinical outcomes in solid tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06748872

NCT06748872 | EPITOME-1015-I: a Study to Investigate ... The study purpose is to establish the safety, tolerability and preliminary efficacy of MDG1015 in patients with epithelial ovarian cancer, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06748872?term=AREA%5BConditionSearch%5D(Synovial%20sarcoma%20OR%20%22sarcoma,%20synovial,%20malignant%22%20OR%20%22%20synovial%20sarcoma%20(disease)%22%20OR%20%22%20Synovialosarcoma%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=7

EPITOME-1015-I: a Study to Investigate the Safety and ... The study purpose is to establish the safety, tolerability and preliminary efficacy of MDG1015 in patients with epithelial ovarian cancer, gastroesophageal ...

4. synapse.patsnap.com synapse.patsnap.com/blog/medigenes-mdg1015-a-third-generation-t-cell-therapy-wins-fda-approval-for-ind-trials

Medigene's MDG1015, a Third-Generation T Cell Therapy ... "In preclinical trials, MDG1015 exhibited potent and sustained T cell-driven anti-tumor activity and the ability to counteract PD-L1-related ...

5. researchgate.net researchgate.net/publication/9068732_NY-ESO-1_and_LAGE-1_Cancer-Testis_Antigens_Are_Potential_Targets_for_Immunotherapy_in_Epithelial_Ovarian_Cancer

(PDF) NY-ESO-1 and LAGE-1 Cancer-Testis Antigens Are ... Antibody to NY-ESO-1/LAGE-1 was present in 11 of 37 (30%) patients whose tumors expressed either NY-ESO-1 or LAGE-1. Detectable antibodies were ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06748872?term=AREA%5BConditionSearch%5D(%22Ovarian%20Disease%22)%20AND%20AREA%5BInterventionSearch%5D(%22Fludarabine%20phosphate%22)&rank=9

EPITOME-1015-I: a Study to Investigate the Safety and ... An adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or ...

7. oncodaily.com oncodaily.com/blog/138168

Medigene Announces U.S. FDA Clearance of IND ... In preclinical studies, MDG1015 has shown strongly enhanced and persistent T cell-driven anti-tumor activity and the ability to mitigate the ...

8. trial.medpath.com trial.medpath.com/clinical-trial/ebd9fe1ba045a435/nct06748872-tcr-t-therapy-mdg1015-ovarian-cancer

a Study to Investigate the Safety and Tolerability of MDG1015 ... The study purpose is to establish the safety, tolerability and preliminary efficacy of MDG1015 in patients with epithelial ovarian cancer, ...