OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS).

person He Huang Zhejiang University Medical School Attached First Hospital, Hangzhou, Zhejiang, China info_outline He Huang, Yongxian Hu, Mingming Zhang, Guoqing Wei, Linghui Zhou, Shan Fu, Jingjing Feng, Ruimin Hong, Jiazhen Cui, Simao Huang, Jincai Zhou, Yu Tang, Xiaomin Ding, Longquan Zhuo, Yanni Zhang, Rick Xu, Xiaowen He

Authors person He Huang Zhejiang University Medical School Attached First Hospital, Hangzhou, Zhejiang, China info_outline He Huang, Yongxian Hu, Mingming Zhang, Guoqing Wei, Linghui Zhou, Shan Fu, Jingjing Feng, Ruimin Hong, Jiazhen Cui, Simao Huang, Jincai Zhou, Yu Tang, Xiaomin Ding, Longquan Zhuo, Yanni Zhang, Rick Xu, Xiaowen He Organizations Zhejiang University Medical School Attached First Hospital, Hangzhou, Zhejiang, China, Department of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, Oricell Therapeutics Co., Ltd., Shanghai, China Abstract Disclosures Research Funding No funding sources reported Background: OriCAR-017 is a novel GPRC5D-targeting CAR T-cells. Previously we had presented early study results (Lancet Haematol 2023: 10: e107–16) following OriCAR-017 treatment, the results of good durable response and long-term safety profile support OriCAR-017 is highly probable to be developed as a promising therapy for patients with relapsed or refractory multiple myeloma. All patients had completed at least 2-year follow-up per protocol. Methods: Ten median age of 64 years (range 41–71) pretreated RRMM pts with a median of 5.5 prior lines therapies (range 3-17) received OriCAR-017. Seven (70.0%) pts were cytogenetics high risk, 4 (40.0%) pts had EMD, 3 (30.0%) pts had ISS stage(III), 2 (20.0%) pts had received prior anti-CD38 and 2 (20.0%) pts were treated with auto-HSCT and 5 (50.0%) pts were treated with BCMA CAR-T. Patients were administrated in a single dose of intravenous OriCAR-017 at 1×10⁶CAR-T/kg (DL1,n=3), 3×10⁶CAR-T/kg(DL2,n=4), or 6×10⁶CAR-T/kg(DL3,n=3). Results: At data cut-off (Jan 16, 2024), all 10 enrolled pts had been evaluated for response with the last patient completed 24 months follow up. ORR was 100.0%, sCR was 80.0%, VGPR was 20.0%. All patients achieved MRD negativity at day 28. The mDOR was 10.43 months (95%CI, 5.00-17.00); mPFS was 11.37 months (95%CI, 5.93-18.00) while mOS has not reached (7 pts still undergo survival follow-up, 1 pt died from disease progress, 2 from COVID). The mDOR was 17.23 months (95%CI, 7.33-NR) and the mPFS was 19.10 months (95%CI, 8.30-NR) with 67% prior BCMA CAR-T pts at high dose level. Nine (90%) pts had grade 1 CRS, and 1 (10%) pt had grade 2 CRS. No ≥ G3 CRS was observed. Median time to CRS onset was 2 days (range 1–9) and median duration was 6 days (range 3–9). No ICANS, nor DLTs were observed. There were no SAE and no treatment-related deaths. No PK difference across dose levels with Cmax 7354.7 copies/μL and AUC 0-28 68587 copies·day/μg. At high doses, CAR-T cells were detectable at 9 months and one responder at 21 months above the LLOQ. The patients with T last ≧9 months had a longer PFS than those with T last <9 months. No correlation of antigen expression and efficacy was observed. All patients had the positive GPRC5D expression in bone marrow CD138+MMPC at baseline, compared with 50% of relapsed pts had a reduced expression measured by flow cytometry. Conclusions: The updated results showed OriCAR-017 continued to provide deep and durable responses, MRD negativity was achieved in all RRMM pts, including in pts refractory to anti-CD38, PIs and IMIDs and failure to BCMA-directed therapy with excellent safety profile. The results of long-term efficacy and safety follow up support that OriCAR-017 is highly probable to be developed as a promising therapy in RRMM. Further clinical development efforts are undertaking to confirm the clinical benefits of OriCAR-017. Clinical trial information: NCT05016778.

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