FT839 in Autoimmune Diseases

An Open-Label, Multicenter, Phase 1/2 Dose-Escalation and Expansion Trial Evaluating the Safety and Efficacy of FT839 in Participants With Autoimmune Diseases

The primary objectives of this trial are to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose of FT839 with or without rituximab and/or background therapy and/or conditioning therapy.

This is a multicenter, Phase 1/2, open-label trial designed to evaluate the safety, pharmacokinetics (PK), anti-B-cell activity, and clinical activity of FT839 in participants with moderate-to-severe ANCA-associated vasculitis (AAV), idiopathic inflammatory myositis (IIM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc).

Participants will receive FT839 as monotherapy or in combination with rituximab, with or without conditioning therapy and/or stable background therapy. Participants will be enrolled in 2 stages during the Phase 1 portion of the trial: a dose-escalation stage and a dose-expansion stage. In the dose-escalation stage, safety and tolerability will be assessed to define the MTD (or through the maximum assessed dose [MAD] in the absence of dose-limiting toxicities [DLTs] defining the MTD). The DLT evaluation period will extend from Day 1 through Day 29. Participants will be followed during the post-treatment follow-up period for up to 2 years after the first dose of FT839, followed by long-term-follow-up for safety and survival for up to 15 years after the first dose of FT839.

In the dose-expansion stage, participants will be enrolled into disease-specific cohorts to further evaluate the safety and activity of FT839.

Following completion of the Phase 1 portion, the Phase 2 portion of the trial will further evaluate the efficacy of FT839 within each disease cohort.

Inclusion Criteria:

• Age ≥18 to ≤70 years
• Must have active B-cell mediated autoimmune disease (AAV, IIM, RA, SLE, or SSc) confirmed by standard criteria
• Moderate to severe disease, requiring at least two prior treatments that were ineffective
• Adequate organ function to tolerate treatment
• Able to provide informed consent and comply with study procedures

Exclusion Criteria:

• Diagnosis of more than 1 disease under study (AAV, IIM, RA, SSc, or SLE) or overlap syndrome
• Women must not be pregnant or nursing
• Severe Organ Dysfunction: Significant heart, lung, liver, or kidney impairment.
• Active or chronic infections
• Active or recent malignancies
• Prior CAR T-cell therapy or organ transplantation
• Known allergies to study treatments
• Body weight <45 kg
• Active central nervous system (CNS) symptoms attributable to autoimmune disease or nonmalignant CNS disease within 12 months prior to trial intervention
• Receipt of any anti-CD19- or anti-CD20-directed therapy within 6 months prior to trial intervention