TPS79 Background: 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 or uncontrolled infection, HIV seropositive status, contraindication to cyclophosphamide, anticipated survival < 3 months, and/or untreated CNS metastases. After screening, leukapheresis is performed, CD8+ and CD4+ T cells are selected, then transduced with the ROR1+ CAR lentivirus and expanded. Lymphodepletion with cyclophosphamide and fludarabine is followed 36-96 hours later by infusion of ROR1 CAR-T cells in escalating doses (3.3 x 105/kg - 1 x 107/kg cells with defined CD8+ and CD4+ composition). Pts are treated in cohorts of 2 to determine cell dose associated with an estimated toxicity rate of < 25%. Primary aim is to determine the maximum tolerated dose (MTD) and safety of ex vivo expanded ROR1 CAR-T cells. Secondary aims include persistence and phenotype of transferred T cells, trafficking of T cells to tumor site, in vivo function, and preliminary antitumor activity of ROR1 CAR-T cells by RECIST 1.1. Dose escalation is determined by CRM algorithm with minimum of 21-day interval following infusion between pts. Preliminary estimates of efficacy will be obtained among all pts and those treated at estimated MTD. Six of 30 pts have been enrolled with no DLTs observed. Clinical trial information: NCT02706392.