Background: The dual CAR-T GC012F developed on the novel FasT CAR-T platform targeting B cell maturation antigen (BCMA), and CD19 was designed to improve depth of response and overall efficacy for CAR-T as therapy for Multiple Myeloma. Here, we present updated data for study (NCT04236011; NCT04182581) including additional pts treated. Methods: From October 2019 to July 2020, 19 heavily pretreated Relapsed/Refractory Multiple Myeloma (RRMM) pts (age 27-71) with a median of 5 prior lines (range 2-9) received a single infusion of GC012F. 94.7% (18/19) were high risk (HR- defined by mSMART), 5 pts had extramedullary disease, 1 pts presented with plasma cell leukemia, and 15/19 were refractory to last therapy. 4/19 pts had received prior anti- CD38, 18/19 pts prior IMiD. 18/19 pts were refractory to PI, 17 pts to IMiD, 3 pts being primary refractory. After lymphodepletion over 2-3 days (30 mg/m²/d, 300mg/ m²/d Flu/Cy) CAR-T cells were administered as single infusion at 3 dose levels: 1x10⁵/kg (DL1) n=1, 2x10⁵/kg (DL2) n=9 and 3x10⁵/kg (DL3) n=9. Results: As of Jan 12, 2021 cut-off, 19 pts were evaluated for response. Overall response rate (ORR) was 94.7% - all responses VGPR or better (94.7% - 16/18 sCR, 2/18 VGPR) with all pts MRD- by flow cytometry (10^-4-10^-6) - earliest response d 28 post infusion. 100% of pts achieved a reduction of paraprotein, 18/19 a 100% reduction. Best response was MRD- sCR in 16/19 patients (84.2%). In DL3 (n=9) 4 additional pts were response evaluable for 6 mth follow-up: 100% (9/9) of pts achieved MRD-sCR as best response, 87.5% (7/8) of response evaluable pts maintained MRD-sCR at landmark analysis of 6 mths. At data cut off, the median time to follow up was 13.8 mths (6.1-16.4) – median duration of response not yet reached. Cytokine Release Syndrome (CRS) and ICANs were graded by ASBMT criteria: grade 1-2 n=16 (84.2%), grade 3 n=2 (10.5%). Median duration of CRS was 4 d (1-8 d). No grade 4/5 CRS or ICANS were observed. 2 deaths occurred on study and were assessed as not related to therapy – one reported previously; one patient was diagnosed with pseudomonas pneumonia on Day 52, refused life-saving treatment and passed. CAR-T median Tmax was 10 d (range 8-14d), median peak copy number (Cmax) was 127548 (16,011-374,346) copies /ug DNA with long duration of persistence of up to 60 weeks at time of data cut off. Patients continue to be monitored for safety and efficacy. Conclusions: BCMA-CD19 dual FasT CAR-T GC012F showed early, deep and durable responses with a high ORR (94.7% - VGPR and better) including a high MRD- sCR rate (DL3=100%, n=9) in high risk RRMM pts including those refractory to anti-CD38, PI and IMIDs with a favorable safety profile consistent with previous findings. BCMA-CD19 dual FasT CAR-T GC012F may present a new treatment approach for patients with RRMM including those with high-risk features refractory to standard of care. Clinical trial information: NCT04236011; NCT04182581