Updated results from inMMyCAR, the ongoing first-in-human phase 1 study of KLN-1010 in patients (pts) with relapsed and refractory multiple myeloma (RRMM).

Abstract

7509 Background: KLN-1010 is a modified lentiviral vector generating a novel, fully human anti-BCMA CAR-T cell in vivo when administered intravenously without preparative chemotherapy to pts with RRMM. Here, we report updated findings from inMMyCAR, the first sponsored, multicenter study of an in vivo CAR-T therapy for pts with RRMM. Methods: Eligibility required RRMM with measurable disease, adequate end-organ and bone marrow (BM) function, and ≥3 prior lines of therapy, including a proteosome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Results: To date, 6 pts were infused across two dose levels (6×10 6 and 2×10 7 IU/kg). Pts ranged in age from 61-72 and had received 3-5 prior lines of therapy. 5 pts had high-risk cytogenetics. BM plasma cell involvement ranged from <5% to 80%. 1 pt had extramedullary disease (EMD). Median time from consent to infusion was 13.5 days. All pts experienced treatment-emergent adverse events. Infusion-related reactions (IRR) occurring in 3 pts (2 at 2×10⁷ IU/kg, 1 at 6×10⁶ IU/kg) were manageable and resolved within 6-48 hrs. Cytokine release syndrome (CRS) was observed in 4 pts, with median onset on day 11 and median duration of 3.5 days; all events were Gr 2 and were managed with tocilizumab and corticosteroids. No immune effector cell–associated neurotoxicity syndrome (ICANS) or delayed neurotoxicity were observed. Peak absolute lymphocyte counts occurred between days 13-22, with median counts of 6.9×10 9 /L (range 2.3-43.1×10 9 /L) and no associated clinical sequelae. CAR-T cells were detectable in peripheral blood through 4 months follow-up and were predominantly memory-phenotype by month 3 (M3). All 6 pts achieved minimal residual disease (MRD) negativity (5 at 10 -6 and 1 at 10 -5 sensitivity) at M1 in the BM. MRD negativity was maintained through M6 (10 -6 sensitivity) in the pt with the longest follow-up. All pts achieved a response by IMWG criteria, and responses deepened over time. The pt with EMD showed complete resolution by M1. Conclusions: Results from inMMyCAR continue to demonstrate compelling early clinical activity. All pts achieved early MRD-negative responses and deepening of IMWG response over time. The pt with the longest follow-up remains MRD-negative with a stringent CR at M6. Activity was also observed in EMD, with radiologic resolution within 1 month. KLN-1010 was generally well-tolerated, with manageable toxicities related to IRR and CRS, supporting potential feasibility for outpatient administration. No ICANS or delayed neurotoxicity were observed. The study remains ongoing; updated results will be presented. Clinical trial information: NCT07075185 . Pt Dose, ×10 7 IU/kg Timepoints of MRD-negative results a IMWG response Duration of follow-up, months 1 2 M1, M3, M6 sCR 6+ 2 2 M1, M3 VGPR 5+ 3 2 M1, M3 VGPR 4+ 4 0.6 M1, M3 VGPR 3+ 5 0.6 M1 sCR 1+ 6 0.6 M1 PR 1+ a By next-gen flow cytometry or sequencing with sensitivity of 10 -5 or 10 -6 .