New data from the Phase 1 THINK clinical trial (NCT03018405) show that two metastatic colorectal cancer (mCRC) patients whose disease progressed following at least two prior therapies had stabilized the disease at a three-month follow-up after receiving the lowest dose level of Celyad’s NKR-2 CAR T-cell therapy.
The third person included in the dose cohort, a pancreatic cancer patient, had disease progression at three months, but the findings suggest that this CAR T-cell therapy induces better results than standard of care, under which the time to disease progression is between 1.9 and 3.2 months.
“We are pleased to have observed these encouraging preliminary results in such a late stage population,” Christian Homsy, Celyad’s CEO, said in a press release. “Despite being dosed only at a tenth of the expected efficacious dose based on animal experiments, the results show a stabilization of the disease. We look forward to the next stages of the trial.”
The open-label THINK trial, conducted in the U.S. and Europe, is a dose escalation Phase 1 study to assess the safety and clinical activity of three administrations of NKR-2 cells across seven cancer types.
The study is designed to include patients with five types of solid tumors (colorectal, ovarian, bladder, triple-negative breast, and pancreatic cancers) and two types of blood cancers (acute myeloid leukemia and multiple myeloma).
Celyad’s NKR-2 CAR T-cell therapy is a personalized therapy that isolates a patient’s own T-cells, a type of white blood cell, and adds a protein called NKG2D to the cells. NKG2D helps T-cells recognize and kill tumor cells. Once they are “armed” with NKG2D, the T-cells are returned to the patient’s circulation.
Pre-clinical studies of NKR-2 CAR T-cells have shown that not only does the treatment kill tumor cells, it also inhibits tumor cells’ activities to avoid destruction by the immune system, promotes an anti-tumor response by the recipient’s immune system, interferes with the blood supply to tumors, and promotes a long-term immune response against the tumor cells.
At each of the three dose levels to be tested in the THINK trial, patients will receive three successive administrations of NKR-2 cells two weeks apart. The dose-escalation part of the study will include up to 24 patients, and an extension phase is planned that would enroll 86 more patients.
“These early results in the two heavily pre-treated mCRC patients are encouraging, considering the dismal clinical outcome of the existing standard of care for this refractory patient population,” said Frédéric Lehmann, vice president of clinical development and medical affairs at Celyad. “Based on these preliminary results, we look forward to progressing our clinical development plan, including higher doses and longer follow-up in the THINK study, as well at starting the SHRINK (CAR-T NKR-2 cells in combination with chemotherapy) and LINK (loco-regional administration) clinical trials shortly.”