Phase I study of immunotherapy for advanced ROR1+ malignancies with autologous ROR1-specific chimeric antigen receptor-modified (CAR)-T cells.

TPS79Background: CAR-T cells have demonstrated marked tumor regression in patients (pts) with hematologic malignancies. ROR1, a tyrosine kinase orphan receptor, is expressed in triple negative breast cancers (TNBC) and non-small cell lung cancers (NSCLC) and is a novel candidate for CAR-T cell therapy. ROR1-specific CAR-T cells are engineered with lentiviral vector encoding ROR1 scFv/4-1BB/CD3ζ and a truncated EGFR molecule to permit elimination of ROR1 CAR-T cells in case of toxicity. Methods: NCT02706362 is a phase I study evaluating the safety and anti-tumor activity of adoptively transferred autologous ROR1 CAR-T cells in pts with advanced ROR1+ TNBC and NSCLC. Eligibility criteria include: metastatic TNBC or NSCLC; measurable disease; prior standard therapy with no maximum on number of prior regimens; tumor ROR1 expression > 20% by IHC; KPS > 70%; age ≥18; negative pregnancy test for women of childbearing potential; informed consent; adequate organ function. Exclusions are: active autoimmune disease ...