Updated results for LEGEND-2 Phase 1/II study of LCAR B38M to treat Multiple Myeloma. Janssen Pharma - Legend Biotech.

The Janssen Pharmaceutical Companies of Johnson & Johnson reported updated results from Legend Biotech Inc.'s LEGEND-2 Phase 1/II open-label study, which evaluated the investigational chimeric antigen receptor T-cell (CAR-T) therapy LCAR B38M in the treatment of patients with advanced relapsed or refractory (R/R) multiple myeloma. The findings, featured in an oral presentation at the 60th American Society of Hematology (ASH) Annual Meeting (Abstract #955), build upon the data from one of four independent institutional studies, the Second Affiliated Hospital of Xi'an Jiaotong University, which were initially presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting and 2017 European Hematology Association (EHA) Meeting.

These updated results showed that the B-cell maturation antigen (BCMA) directed CAR-T cell therapy LCAR B38M achieved deep and durable responses, with a manageable and tolerable safety profile in patients who failed a median of three prior therapies.

LCAR B38M identifies the investigational product being studied in China and JNJ-68284528 identifies the investigational product being studied in the U.S./EU, both of which are representative of the same CAR-T therapy.

In this study update, 57 patients with advanced R/R multiple myeloma received LCAR B38M CAR-T cell therapy. The median age of the patients was 54 years (range, 27�72); median number of prior therapies was three (range, 1�9); and 74 percent of patients had Stage 3 disease by Durie-Salmon staging. According to study findings, there was an 88 percent overall response rate (ORR) (95 percent confidence interval [CI]: 76-95). Complete response (CR) was achieved by 74 percent of patients (95 percent [CI]: 60-85); very good partial response (VGPR) was achieved by four percent of patients and partial response was achieved by 11 percent of patients. Notably, among 42 patients with CR, 39 patients (68 percent) were minimal residual disease (MRD) negative in the bone marrow as measured by 8-color flow cytometry. With a median follow-up of 12 months, the median duration of response (DOR) was 16 months (95 percent [CI]: 12-not reached [NR]) and a median progression-free survival (PFS) of 15 months for all patients was observed. Among the patients who achieved an MRD negative CR, the median PFS was 24 months.

The most common adverse events (AEs) were pyrexia (91 percent), cytokine release syndrome (CRS) (90 percent), thrombocytopenia (49 percent) and leukopenia (47 percent). In patients who experienced Grade 3/4 AEs (65 percent), the most common were leukopenia (30 percent), thrombocytopenia (23 percent) and increased aspartate aminotransferase (21 percent). CRS was mostly Grade 1 (47 percent) and 2 (35 percent). However, four patients (seven percent) experienced Grade 3 CRS. The median time to onset of CRS was nine days (range, 1�19). All but one of the CRS events resolved, with a median duration of nine days (range, 3�57). Neurotoxicity was observed in one patient who had Grade 1 aphasia, agitation and seizure-like activity. Overall, 17 patients died during the study and follow-up period; causes of death were progressive disease (PD; n=14), suicide after PD (n=1), esophagitis (n=1) and pulmonary embolism and acute coronary syndrome (n=1).

LEGEND-2 (NCT03090659) is an ongoing Phase 1/II, single-arm, open-label program in China comprised of four independent institutional studies being conducted at participating hospitals evaluating the efficacy and safety of LCAR B38M for the treatment of patients with R/R multiple myeloma.

Comment: Legend and Janssen Pharma plan a Phase II U.S. trial which has an estimated enrollment of 60 participants and a primary completion scheduled for July 2020.