Mipetresgene autoleucel (Mip-cel) for NY-ESO-1–positive synovial sarcoma

Multi-center Study of TBI-1301 (INN: Mipetresgene Autoleucel; Mip-cel) in Patients With NY-ESO-1 Positive Synovial Sarcoma

This trial will test whether mipetresgene autoleucel (Mip-cel), a NY‑ESO‑1–targeted T‑cell therapy given after cyclophosphamide and fludarabine, can shrink tumors or control disease in adults with NY‑ESO‑1–positive synovial sarcoma.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Takara Bio Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine
• Locations: 2 sites (Osaka, Osaka and 1 other locations)
• Trial ID: NCT07174427 on ClinicalTrials.gov

What this trial studies

This multicenter Phase 3 trial administers cyclophosphamide and fludarabine lymphodepletion followed by infusion of TBI-1301 (mipetresgene autoleucel), an autologous T‑cell receptor gene therapy targeting NY‑ESO‑1. Eligible adults have unresectable or recurrent synovial sarcoma that expresses NY‑ESO‑1 and are HLA‑A*02:01 or HLA‑A*02:06 positive, with 1–4 prior systemic chemotherapy regimens and measurable disease per RECIST 1.1. Patients undergo leukapheresis to collect T cells for ex vivo genetic modification and expansion before infusion. The study monitors safety and antitumor activity to determine whether this approach produces meaningful responses with an acceptable safety profile.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed, unresectable or recurrent synovial sarcoma that is NY‑ESO‑1–positive, HLA‑A*02:01 or HLA‑A*02:06 positive, who have received 1–4 prior chemotherapy regimens, have measurable disease, ECOG 0–2, and adequate organ function are ideal candidates.

Not a fit: Patients whose tumors do not express NY‑ESO‑1, who lack the required HLA type, who have resectable disease, significant organ dysfunction, or very limited life expectancy are unlikely to benefit.

Why it matters

Potential benefit: If successful, Mip-cel could produce tumor shrinkage and durable remissions for a subset of patients with treatment‑refractory NY‑ESO‑1–positive synovial sarcoma.

How similar studies have performed: Earlier phase trials of NY‑ESO‑1–directed TCR T‑cell therapies have shown objective responses in synovial sarcoma, but larger studies are needed to confirm durability and safety.

Eligibility criteria

Inclusion Criteria:

1. ≥ 18 years of age
2. Histologically confirmed synovial sarcoma
3. Surgically unresectable tumor
4. Progressing or recurrent synovial sarcoma which has been treated with 1-4 regimens of systemic chemotherapies including anthracycline
5. HLA-A\*02:01 or HLA-A\*02:06 positive
6. Tumor that express NY-ESO-1 by immunohistochemistry
7. Measurable lesions that are evaluable by the RECIST ver1.1
8. ECOG Performance Status of 0, 1 or 2
9. No treatment such as chemotherapy and be expected to recover fully from the previous treatment at the time of the lymphocytes collection for manufacturing
10. Life expectancy ≥ 16 weeks after consent
11. No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc) and meet the following lab value criteria; Total bilirubin ≤ 1.5 x upper limit of normal (ULN); AST(GOT), ALT(GPT) \< 3.0 x ULN; Creatinine \< 1.5 x ULN; 2,500/μL \< WBC ≤ULN; Hemoglobin ≥ 8.0g/dL; Platelets ≥ 75,000/μL
12. Patients must be able to understand the study contents and to give a written consent at his/her free will.

Exclusion Criteria:

1. Patients with the following conditions are excluded from the study; Unstable angina, cardiac infarction, or heart failure; Uncontrolled diabetes or hypertension; Active infection; Obvious interstitial pneumonia or lung fibrosis by chest X-ray; Active autoimmune disease requiring steroids or immunosuppressive therapy.
2. Active metastatic tumor cell invasion into CNS
3. Active multiple cancer
4. Positive for HBs antigen or HBV-DNA observed in serum
5. Positive for HCV antibody and HCV-RNA observed in serum
6. Positive for antibodies against HIV or HTLV-1
7. History of serious hypersensitivity reactions to bovine or murine derived substances.
8. History of hypersensitivity reaction to ingredients or excipients of investigational drugs used in this study
9. History of hypersensitivity reaction to antibiotics used in manufacturing for the investigational drug used in this study.
10. History of treatment with cell therapy or gene therapy
11. Alcohol or drug dependence that may interfere with study participation
12. Pregnant females, lactating females (except when they cease and do not resume lactation) or female and male patients who cannot agree to practice the adequate birth control from the consent to 6 months after infusion of the investigational drug.
13. Clinically significant systemic illness that in the judgment of the PI or sub-investigator would compromise the patient's ability to tolerate protocol therapy or significantly increase the risk of complications.

Where this trial is running

Osaka, Osaka and 1 other locations

• Osaka International Cancer Institute — Osaka, Osaka, Japan (Recruiting)
• Kyusyu University Hospital — Fukuoka, Japan (Recruiting)

Conditions Synovial Sarcomas; adoptive cell transfer; NY-ESO-1; T cell receptor; ex vivo gene therapy; synovial sarcoma