A Phase I/II Study of FG-M131 in TRBC1+ Relapsed/Refractory Peripheral T-Cell Lymphoma

FG-M131 for injection is an antibody-drug conjugate (ADC) targeting the T-cell receptor beta chain constant region 1 (TRBC1). TRBC1 is a subunit of the αβ T-cell receptor (TCR) complex. Targeting TRBC1 can eliminate TRBC1-positive malignant T cells while sparing TRBC2-positive normal T cells, providing a novel strategy for the treatment of T-cell malignancies. This study is a multicenter, open-label Phase I/II clinical trial in patients with TRBC1-positive relapsed/refractory peripheral T-cell lymphoma, designed to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity of FG-M131 for injection in this patient population. The study consists of a Phase I dose-escalation stage and a Phase IIa cohort-expansion stage.

Inclusion Criteria: * Voluntarily sign the informed consent form, understand the study, are willing to comply with and have the ability to complete all trial procedures; * Age 18-75 years (inclusive), any gender; * Histologically and/or cytologically confirmed peripheral T-cell lymphoma or cutaneous T-cell lymphoma; * Relapsed or refractory lymphoma after at least one prior line of therapy； * Able to provide tumor tissue specimens; * ECOG performance status of 0 or 1; * Expected survival ≥3 months; * Have at least one measurable tumor lesion; * Adequate cardiac, bone marrow, liver, renal function; Exclusion Criteria: * Have received a live vaccine within 3 months prior to the first dose; * Have received radiotherapy within 4 weeks prior to the first dose; * Have received other anti-tumor drug therapy within 3 weeks or within 5 half-lives of the anti-tumor drug prior to the first dose; * Have undergone major surgery within 4 weeks prior to the first dose; * Have previously received any therapy targeting the TRBC1 antigen or any antibody-drug conjugate with MMAE payload; * Have received autologous stem cell transplantation within 3 months prior to the first dose; * Have previously received allogeneic stem cell transplantation; * Have a history of other malignancies within 5 years prior to the first dose; * Have received high-dose systemic vitamin A therapy (daily dose \>15,000 IU \[i.e., 5,000 mcg\]) within 3 weeks prior to the first dose of study drug; * Have any condition requiring systemic treatment with corticosteroids (\>20 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose; * Have received oral retinoid drugs for any indication within 3 weeks prior to the first dose; * Have adverse reactions from prior treatments that have not recovered to CTCAE v5.0 Grade ≤1 (excluding alopecia and anemia) prior to the first dose; * Presence or history of central nervous system lymphoma, leptomeningeal disease, or spinal cord compression; * Have a history of severe allergic reactions or are allergic to the investigational drug; * Have experienced a clinically significant cardiac disease within 6 months before the first dose; * Have uncontrolled systemic diseases assessed by the investigator, including diabetes, hypertension, pulmonary fibrosis, interstitial lung disease, etc.; * Known history of Hepatitis C or chronic active Hepatitis B; * Clinically uncontrolled diseases such as diabetes mellitus, thyroid disease, or other severe systemic diseases requiring systemic treatment; * Active or progressive infection requiring systemic therapy within 2 weeks prior to the first dose; * Known or suspected active autoimmune disease requiring systemic therapy within 2 years prior to the first dose; * Are pregnant or breastfeeding;