us zamto-cel autoimmune diseases

Conditions: Lupus Nephritis; Systemic Lupus Erythematosus; Systemic Sclerosis (SSc); Diffuse Cutaneous Systemic Sclerosis

Summary: aid is a phase i multi-cohort study to assess the safety and tolerability of zamtocabtagene autoleucel (zamto-cel) in patients with refractory autoimmune diseases (sle-non renal, sle-ln, ssc/dcssc) after receiving standard therapy.

this is a phase 1, multicohort, dose-finding study evaluating autologous t cells engineered to target dual cd19 and cd20 antigens in subjects with refractory autoimmune diseases following standard therapy. the investigational product, zamto-cel, is a chimeric antigen receptor t-cell (car-t) therapy genetically engineered to enable subjects' t cells to express cars on their surfaces. eligible subjects will undergo leukapheresis for the collection of cells required for manufacturing. prior to infusion of the fresh car-t product, subjects will receive a lymphodepleting regimen consisting of cyclophosphamide and fludarabine. the car-t cell infusion will be administered intravenously at a dose of 2.5 x 10\^6 or 1.0 x 10\^6 car+ cells/kg body weight, based on the dose level assigned to the cohort. the study will initially enroll 3 subjects per cohort in a staggered manner to evaluate safety. upon confirmation of safety, the study will proceed to cohort-specific recommended phase 2 dose (rp2d) and dose expansion phases. subjects will be monitored for up to 1 year to assess safety, preliminary efficacy, and health-related quality of life (hrqol). additional long-term follow-up will be conducted under a separate long-term follow-up protocol.

Eligibility criteria:
general key inclusion/exclusion criteria across all cohorts inclusion criteria: •confirmed diagnosis of autoimmune disease (sle-non-renal, sle-ln, ssc/ dcssc) exclusion criteria: * prior gene therapy treatment * active malignancy within past 5 years * significant active fungal or bacterial infection * history or presence of cns lupus or other cns disease * egfr \< 45 ml/min/1.73 m\^2 * total bilirubin outside the normal range (unless congenital hyperbilirubinemia such as gilbert syndrome has been confirmed). systemic lupus erythematosus-non-renal key inclusion/exclusion criteria inclusion criteria: * positive for at least 1 of the following autoantibodies at screening: anti- double stranded dna or anti-smith * systemic lupus erythematosus disease activity index-2000 score ≥ 8 and at least 1 british isles lupus assessment group (bilag)-2004 class a (severe manifestation) organ scores * inadequate response to glucocorticoids and to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, or obinutuzumab exclusion criteria: * subjects with neuropsychiatric sle. * drug-induced sle. systemic lupus erythematosus - lupus nephritis key inclusion/exclusion criteria inclusion criteria: * positive for at least 1 of the following autoantibodies at screening: anti- double stranded dna or anti-smith * confirmed ln diagnosis by kidney biopsy during screening or within the previous 6 months, with severe active phase of the disease. * progressing despite maintenance on maximally tolerated doses of renin- angiotensin system (ras) blocking agents, unless allergic to or intolerant of ace inhibitors and arbs * inadequate response to glucocorticoids and hydroxychloroquine and at least 1 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid derivatives, belimumab, azathioprine, methotrexate, rituximab, obinutuzumab, calcineurin inhibitor (cyclosporin, tacrolimus or voclosporin) exclusion criteria: •evidence of rapidly progressive glomerulonephritis (defined as a doubling of serum creatinine within 3 months prior to enrollment) or as determined by the study investigator. systemic sclerosis/diffuse cutaneous systemic sclerosis cohort key inclusion/ exclusion criteria inclusion criteria: * active disease defined as: * modified rodnan skin score (mrss) ≥ 16 units, in the prior 6 months, with 1 or more of the following: * increase in mrss by ≥ 3 units or 10% * involvement of 1 new body area with increase in mrss by ≥ 2 units * involvement of 2 new body areas with increase by ≥ 1 mrss unit or * progressive interstitial lung disease (ild) defined as: - worsening of respiratory symptoms and an increased extent of fibrosis evaluated by high-resolution computed tomography * lack of response to standard therapy (e.g., failure of ≥ 2 immunosuppressive therapies) exclusion criteria: * "active" gastric antral vascular ectasia, as evidenced by bleeding (ie, on esophagogastroduodenoscopy) in the past 6 months or as per investigator's assessment. * history of ssc renal crisis within 1 year prior to screening; presence of kidney impairment due to conditions other than ssc

Keywords: chimeric antigen receptor car t zamtocabtagene autoleucel autoimmune disease immune system diseases sle-non renal sle-ln ssc dcssc lupus