Celyad’s new trial evaluating the effectiveness and safety of its drug candidate NKR-2 (a CAR T-cell therapy) in seven cancer types, including ovarian cancer, has been approved to start in Belgium.

CAR T-cells are immune cells isolated from each patient that are genetically modified to gain a better capacity to identify and kill cancer cells based on the proteins they express at their surface.

Celyad’s NKR-2 therapy allows lymphocytes, a type of immune cells, to express the human NK receptor NKG2D. When cancer cells expressing molecules recognized by NKG2D, the receptor becomes activated and triggers death mechanisms in those cells.

Importantly, 80 percent of tumors express eight naturally occurring molecules that activate this receptor, which makes NKG2D a promising therapeutic tool.

The new Phase 1b trial, called THINK, was designed to evaluate the effectiveness and safety of multiple doses of NKR-2 T-cells in seven refractory types of cancer. These include five solid tumors (ovarian, colorectal, bladder, triple-negative breast, and pancreatic cancers), and two blood cancers (acute myeloid leukemia and multiple myeloma).

THINK will be carried out both in the U.S. and in Europe and includes two phases:

• Dose escalation phase: This will include up to 24 patients with the seven types of cancer, which will receive NKR-2 T-cells in a dose that’s dependent on their body weight. At each dose, NKR-2 T-cells will be administered every two weeks, in three successive administrations.
• Extension phase: This part of the study will included 86 additional patients. The effect of NKR-2 T-cells will be evaluated independently for each cancer type.

Previous studies have shown that NKR-2 therapy not only causes cancer cells to die, it also prevents cancer cells from hiding from the immune system, activates more immune cells, and inhibits blood supply to the tumor, thereby blocking its survival in multiple ways. The NKR-2 therapy appears to promote a better and more durable immunity against cancer cells expressing the specific molecules recognized by NKG2D.

While other CAR T-cell therapies usually require that patients undergo prior lymphodepletion treatment — a type of chemotherapy treatment to eliminate the patient’s lymphocytes and allow the growth of the new CAR T-cells — the NKR-2 therapy does not. This allows the immune system to remain intact and patients do not experience toxicities associated with chemotherapy.

“We are excited to initiate this multiple tumor study with key cancer institutions in Belgium,” Frédéric Lehmann, vice president of clinical development and medical affairs at Celyad, said in a news release.

“While immunotherapy is rapidly transforming the treatment of patients with cancer, there remains a significant unmet medical need for more effective therapies. It is our hope that Celyad’s NKR-2 T-cells have the potential to be truly disruptive in the way we treat cancer and this study is one more step towards that goal,” he said.