CTCL, PTCL, TRBC1 ADC
Conditions
Keywords
PTCL, TRBC1 ADC, CTCL
Brief summary
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.
Interventions
DRUGFG-M131
Accelerated titration method, IV infusion Q3W; Adaptive BOIN design, IV infusion Q3W. (21-day cycles)
Sponsors
FutureGen Biopharmaceutical (Beijing) Co., Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety assessed by Adverse Events (AEs) | Up to 24 months | Incidence and severity of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
| Maximum Tolerated Dose (MTD) | 21 days | MTD |
| Objective Response Rate (ORR) | Up to 24 months | ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation. |
| Complete Response Rate (CRR) | Up to 24 months | CRR is defined as the proportion of participants who have a best overall response of Complete Response (CR) as assessed by investigator evaluation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 24 months | PFS is defined as the duration from randomization to the first imaging confirmation of progressive disease by investigator evaluation or death due to any cause (whichever occurs first). |
| Duration Of Response (DOR) | Up to 24 months | DOR is defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by investigator evaluation or death due to any cause (whichever occurs first). |
| Overall Survival (OS) | Up to 24 months | OS is defined as the time from randomization to deathdue to any cause. |
| Maximum measured plasma concentration of FG-M131 | Up to 24 months | Cmax |
| Time to maximum plasma concentration of FG-M131 | Up to 24 months | Tmax |
| Half-life of FG-M131 | Up to 24 months | T1/2 |
| ADA | Up to 24 months | Incidence of anti-FG-M131 antibody and/or neutralizing antibody positivity |
Countries
China
Contacts
CONTACTZhaoyu Jin
Outcome results
None listed