Pivotal Year Looms for CAR T-Cell Therapies

Andrew D. Smith | March 01, 2017
Steven A.
Rosenberg, MD, PhD

Steven A. Rosenberg, MD, PhD

Chimeric antigen receptor (CAR) T-cell therapies have already produced clinical trial results that—even by the lofty standards set by emerging immunotherapies—have been stunning. This year should demonstrate whether the most tested treatments in the class perform as well in real-world patients and whether new agents can produce similarly spectacular trial results against a wider variety of cancers.

Kite Pharma has initiated a rolling submission with the FDA for permission to market KTE-C19 (axicabtagene ciloleucel) for use in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant.1 The new drug application will rest largely on the strength of the ZUMA-1 trial, which produced an objective response rate (ORR) of 91% and a complete remission (CR) rate of 73%.2

Novartis, meanwhile, plans to seek FDA approval early this year to market CTL019 (tisagenlecleucel- T) to pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL).3 That application will hinge on the positive results of the phase II ELIANA trial, which, according to an oral presentation at the 2016 American Society of Hematology (ASH) Annual Meeting, produced a CR or a CR with incomplete blood count recovery (CRi) in 82% (41 of 50) patients with B-cell ALL.

The FDA awarded breakthrough therapy designations to both medications on grounds that they address unmet needs.4 The agency also is evaluating two CAR T-cell therapies from Juno Therapeutics, JCAR017 and JCAR015, through the breakthrough therapy program, which is aimed at prioritizing reviews of promising drugs.4

Development plans for JCAR015 in adult patients with relapsed/refractor B-cell ALL have been in flux since November 2016 when Juno Therapeutics voluntarily placed the phase II ROCKET trial on hold after 2 patients, like 3 other participants before them, died from cerebral edema.5 The hold does not affect the company’s efforts to develop JCAR017 or other CAR T-cell therapies.

Other companies seeking to bring CAR therapies to market include:

• Bluebird Bio is working with Celgene to conduct a phase I trial of its lead CAR T candidate, bb2121, in patients with relapsed and refractory multiple myeloma.6 It also reports several other T-cell receptor (TCR) adoptive immunotherapy candidates in preclinical stages of development.7

• Cellectis has begun phase I trials of its lead therapy, UCART19, in patients with ALL and chronic lymphocytic leukemia (CLL)8 and has asked the FDA for permission to launch phase I trials of UCART123 in patients with acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm.9

• Adaptimmune and partner GlaxoSmithKline are conducting early-stage trials of NY-ESO TCR in patients with synovial sarcoma, multiple myeloma, melanoma, ovarian cancer and non– small cell lung cancer (NSCLC). The company has also launched a phase I trial of MAGE-A10 TCR in NSCLC and is about to begin testing the treatment against melanoma as well as cancers of the bladder, head and neck.10

Scope of New Therapies

If these novel CAR therapies prove successful, the treatments could provide extra years of life for real-world patients. That would be great news for patients, particularly those with recurrent and incurable hematological cancers, which are the current focus of most companies.

“There is definitely reason for optimism that CAR-T treatments will prove effective against a wide range of hematological cancers. There are a number of B-cell malignancies that express the CD19 antigen that it targeted in most of the treatments that have done so well in trials to date, and we’re starting to see some evidence that CAR-T therapies with alternate targets or alternate vectors may work against a number of CD19- negative malignancies,” said Charles Mullighan, MD, chairman of ASH’s Committee on Scientific Affairs.

“Of course, it will be several years until we know for sure how big an impact CAR-T will have on hematology as a whole, but we are already seeing this as a major new weapon in our arsenal against relapsed or refractory ALL,” he said. Meanwhile, efforts to engineer CAR T-cell therapies for use against solid tumors continue. New targets for CAR therapies in solid tumors and a greater understanding of the differences in their activity compared with hematologic malignancies is needed, researchers have said.11


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 1st Annual European Congress on Immunotherapies in Cancer™Dec 13, 20171.5
Community Practice Connections™: The Emergence of CAR-T Cell Therapy for Hematologic Malignancies: Moving From Bench to BedsideDec 29, 20171.5
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