Background: GC012F is a chimeric antigen receptor (CAR)-T cell therapy with B cell maturation antigen (BCMA) and CD19 dual-target developed on the novel FasT CAR-T platform enabling 22-36 h manufacturing. Our previous results were presented at ASCO and EHA 2022 for 29 pts (NCT04236011; NCT04182581), which demonstrated GC012F treatment led to deep and durable response in RRMM pts. Furthermore, initial results showed that GC012F showed considerable efficacy and safety in high-risk transplant-eligible newly diagnosed MM pts (Blood 2022; 140 (Supplement 1): 889–890). Here we present update on RRMM study with a longer median follow-up. Methods: From October 2019 to January 2022, 29 heavily pretreated RRMM pts (age 27-76) with a median of 5 prior lines therapies (range 2-9) received GC012F. 26 (89.7%) pts were high risk (HR- mSMART), 8 (27.6%) pts had EM disease, 24 (82.8%) pts were refractory to last therapy. 10 (34.5%) pts had received prior anti-CD38 and 11 (37.9%) pts were treated with auto-HSCT. After lymphodepletion over 2-3 days (30 mg/m²/d, 300mg/m²/d Flu/Cy), GC012F was administered as single infusion at 3 dose levels: 1x10⁵/kg (DL1) n=2, 2x10⁵/kg (DL2) n=10 and 3x10⁵/kg (DL3) n=17. Results: At the time of data cut-off (January 30, 2023), 29 eligible pts had been evaluated for response with the last patient completed 12 months efficacy follow up. Overall response rate was 93.1% (27/29), stringent complete response rate was 82.8% (24/29), ≥very good partial response rate was 89.7% (26/29). All patients dosed (29/29) achieved MRD negativity by flow cytometry (sensitivity 10^-4-10^-6). To date 24/29 patients (82.8%) achieved MRD- sCR across all dose levels. According to the Kaplan-Meier method, the median duration of response (DOR) was 37.0 months (95%CI, 11.0-NR) and the median progression free survival (PFS) was 38.0 months (95%CI, 11.8-NR). Cytokine Release Syndrome (CRS) was reported in 25 (86.2%) pts, which was mostly ≤grade 2 (n=23, 79.3%) and 2 (6.9%) pts were grade 3. No ICANS was observed (Graded by ASBMT criteria). Median duration of CRS was 3 days (1-8 d). PK results showed no difference amongst dose levels DL1 to DL3. The median time of persistence was 410 days (range: 51-1183) and GC012F was still detectable in 23 (79.3%) pts at 6 months and in 16 (55.2%) pts at 12 months after infusion. sBCMA plasma levels started declining at day 4 in 80% (8/10) patients, falling sharply at day 10 in 100% (19/19), and reaching minimal levels from 30 to 60 days post infusion in 100% (29/29) patients. Conclusions: The updated results showed GC012F continues to provide deep and durable responses, and a very high MRD negativity ratein RRMM pts, including in pts refractory to anti-CD38, PIs and IMIDs. Based on these promising results of the study of GC012F for RRMM, further clinical studies will be conducted to confirm the efficacy of GC012F. Clinical trial information: NCT04236011; NCT04182581.