Single-center phase 1 study of ROR1-specific CAR-T cells for advanced hematopoietic and epithelial malignancies

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is expressed in hematopoietic and epithelial cancers but has limited expression on normal adult tissues. A phase 1 study at Fred Hutchinson Cancer Center (Seattle, WA) evaluated ROR1-specific CAR-T cells for advanced ROR1-positive chronic lymphocytic leukemia (CLL; n=3), triple-negative breast cancer (TNBC; n=10), and non-small cell lung cancer (NSCLC; n=8). After lymphodepletion was cyclophosphamide/fludarabine or oxaliplatin/cyclophosphamide, patients received CAR-T cells at dose levels from 3.3 x 10⁵ to 1 x 10⁷ cells per kg body weight.Treatment was well tolerated, apart from one dose-limiting activity with the highest dose level in a NSCLC patient. Two of the three (66.7%) CLL patients showed robust CAR-T cell expansion and a rapid antitumor response. In patients with NSCLC and TNBC, Car-T cells expanded to variable levels and infiltrated tumors poorly, with partial response in one patient (5.5%). The authors conclude that ROR1-specific CAR-T cells were well tolerated in most patients, with antitumor activity in CLL, but only limited activity in TNBC and NSCLC.