September / October 2017

In Good Company


The success of Novartis’s CTL019 in treating relapsed or refractory pediatric ALL, including FDA approval of the company’s biologics license application, makes it the first adoptive cell therapy to reach the market. While Novartis is also seeking approval of CTL019 from the FDA and the EMA for another disease, diffuse large B-cell lymphoma in adults, 7 there are many other CAR T-cell products in development and clinical trials.

One contender is Kite Pharma’s KTE-C19 (axicabtagene ciloleucel). Originally developed at the National Cancer Institute (NCI), 1 this CAR T-cell therapy also targets the CD19 antigen on B-cells and is in clinical trials for patients with refractory aggressive non-Hodgkin lymphoma (NHL). In a phase 2 study, 36% of patients were cancer-free at six months.2 KTE-C19 received priority review from the FDA earlier this year; the agency plans to announce its decision on whether to approve the drug 29 November. 3 Kite Pharma also filed a marketing authorization application with the EMA for KTE-C19 in July 2017, the first CAR T-cell therapy application in Europe.

KTE-C19 is also in phase 2 trials for the treatment of ALL in both adults and children, with data due in 2018. The adult trial has shown promising results, with 73% of patients having complete remission. 12 Another phase 2 study is testing the drug for the treatment of mantle cell lymphoma, which accounts for 6% of NHL cases.1

Juno Therapeutics had a major setback during the phase 2 trial of its lead candidate JCAR015, when three patients died. After a reset, two more patients died and the company pulled the plug on the study. 4 Juno has other CAR T-cell products in phase 1 and 2 clinical studies for the treatment of NHL, ALL, and multiple myeloma. 5 One of these, JCAR017, has shown positive response data in NHL, but the experimental treatment was linked to one death and severe neurotoxicity in 18% of patients. 6

Another promising target for CAR T-cells is the B-cell maturation antigen (BCMA), expressed on mature B lymphocytes, with the potential to treat multiple myeloma. Nanjing Legend Biotech presented promising phase 1 results for its candidate LCAR-B38M at the annual meeting of the American Society of Clinical Oncology in June.8 Another contender is Bluebird Bio, whose partner Celgene had good phase 1 data for its anti-BCMA drug bb2121. This includes positive safety data with no moderate or severe CRS or neurotoxicity observed.9

While biotechnology and pharmaceutical companies are joining forces to develop and bring CAR T-cell products to market, many academic institutions continue experiments that are key to development.10 In addition to its success with CTL019, the University of Pennsylvania is partnering with Novartis to develop a CAR T-cell construct that targets the epidermal growth factor receptor EGFRvIII antigen for the treatment of recurrent glioblastoma, a solid brain cancer tumor that currently has no curative treatment.11 Significant progress is also being made at the NCI, Memorial Sloan Kettering, Fred Hutchinson, and Baylor College of Medicine in developing CAR T-cell therapies.