First in Human Study of NVG-111 in Relapsed/Refractory ROR1+ Malignancies

Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is a protein which is expressed at high levels on many types of cancers but is absent or expressed at low levels in normal adult organs. NVG-111 is a bispecific antibody T cell engager, comprising tandem single chain variable fragments (scFv), one arm binding to ROR1 on cancer cells, the other to cell surface CD3 on lymphocytes. Dual binding of NVG-111 causes MHC-independent immunological synapse formation, releasing perforins, granzyme B and cytokines, resulting in targeted killing of the cancer cells. This is a Phase 1 first in human study to assess the safety, pharmacokinetics and efficacy of NVG-111 in patients with subjects with relapsed/refractory ROR1+ malignancies. A range of doses will be studied in sequential cohorts to understand safety, pharmacokinetics and pharmacodynamics of the drug and establish the recommended phase 2 dose (RP2D). At each dose level, patients will receive 3 cycles of NVG-111 by continuous intravenous infusion, each cycle consists of 21 days treatment. Additional cycles may be given depending on the response seen. All patients will have a safety follow up visit 4 weeks after completion of treatment with NVG-111, and will then enter long term follow up for up to two years to evaluate the duration of efficacy.