InMMyCAR phase I: Novel in vivo CAR T-cell gene therapy for RRMM

Preliminary results from inMMyCAR (NCT07075185), a first-in-human phase I trial investigating KLN-1010, a novel gene therapy generating anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells in vivo, in patients with relapsed/refractory multiple myeloma (RRMM), were presented by Phoebe Joy Ho at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US. KLN-1010 is a modified, replication-incompetent, self-inactivating lentiviral vector. Unlike traditional CAR T-cell therapy, KLN-1010 employs an intravenously delivered approach that programs a patient's own T cells in vivo to express a CAR, eradicating the need for apheresis, ex vivo manufacturing, and lymphodepleting chemotherapy.

Eligible patients (N ~ 20) had RRMM after ≥3 prior lines of therapy (LoT), including a proteasome inhibitor, an immunomodulator, and an anti-CD38 monoclonal antibody. The primary endpoints were safety, tolerability, and the recommended phase II dose (RP2D). Secondary endpoints were CAR T-cell expansion and persistence, overall response rate (ORR), minimal residual disease (MRD), duration of response (DoR), and progression-free survival (PFS). Results from four patients are reported (n = 3 dose level [DL] 1; n = 1 DL –1).

Key data: Increases in CAR+ T cells by Day 15 were seen in all 4 patients (22%, 35%, 72%, and 85% increases, respectively). All patients displayed phenotypic evidence of persistent memory CAR T-cell formation in the blood and bone marrow after KLN-1010 treatment, with the level of CAR T-cell expansion being commensurate with approved CAR T-cell therapies. All patients achieved MRD negativity by Month 1 (n = 3 at 10⁻⁶ sensitivity; n = 1 at 10⁻⁵ sensitivity), with sustained MRD-negative bone marrow responses at 3 months in the first two patients with longest follow-up. Immune effector cell-associated neurotoxicity syndrome (ICANS)/delayed neurotoxicity and cytokine release syndrome (CRS) were reported in zero and three patients (all Grade 1–2), respectively, with few reports of cytopenia.

Key learning: KLN-1010 demonstrates promising clinical safety and efficacy comparable with approved ex vivo CAR T-cell therapies, supporting the continued evaluation of in vivo CAR T-cell therapies for patients with RRMM.