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

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

Inclusion criteria

• 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)

Exclusion criteria

• 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:

• Positive history of esophageal or gastric resection that the Investigator considers is at increased risk of bleeding or perforation