Most companies developing CAR-T therapies are firmly focused on blood cancers, but Belgian biotech Celyad is bucking the trend with a trial that will include a tougher challenge—solid tumors.
Celyad has just recruited the second patient in its THINK trial of its CAR-T candidate NKR-2, which will assess the therapy in five solid tumors, as well as hematological cancers acute myeloid leukemia (AML) and multiple myeloma (MM).
The patient has pancreatic cancer and will receive three doses of CAR-T cells, according to the company, which intends to enroll around 14 patients per cancer type in the phase 1b trial. The first patient to be enrolled had colorectal cancer. Clinical results are expected in the first half of next year.
Dr. Frédéric Lehmann, vice president of clinical operations and medical affairs at Celyad, said that the company's preclinical work has "generated impressive results in models of pancreatic cancer, a particularly devastating form of the disease with a mortality rate that has remained largely unchanged in recent decades."
Analyst Dr. John Savin at Edison said that there are a few trials of CAR-T in solid tumors, but "otherwise this large potential market is not being addressed by active clinical development" and Celyad has "a lead position" in the category.
Among Celyad's rivals in the CAR-T space, Kite Pharma and Novartis are vying to get candidates approved this year but are both starting out with programs in hematological malignancies, focusing on diffuse large B-cell lymphoma and acute lymphoblastic leukemia, respectively.
"A major drawback with the current CAR CD19 focus of other companies is that, while it is excellent for B-cell tumours (like leukaemias and lymphomas), CD19 will not target other cancers," said Savin in a research note.
"With the advantage of the NKG2D mechanism of cell targeting used by NKR-2, Celyad is able to run the THINK trial in multiple cancer types," he added, although he cautioned that this broader activity could raise the risk of side effects.
Celyad's first phase 1 trial of NKR-2 was conducted in AML and MM and despite low doses of cells showed encouraging activity, with one AML patient showing no disease progression and improved blood measurements after 12 weeks.
The new trial will use a dose of NKR-2 that is an order of magnitude higher than in the earlier study and along with AML, MM and pancreatic cancer will also include patients with colorectal, ovarian, bladder and triple-negative breast cancer.
Other CAR-T trials in solid tumors include Bellicum's phase 1 study in advanced pancreatic cancer with an anti-PSCA CAR construct, due to complete in 2020, and a National Cancer Institute melanoma study using CD4 CAR T cells targeted to the MAGE antigen, according to Edison.