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Clinical Trials

Date: 2018-09-05

Type of information: update on patient enrollment

phase: 1b

Announcement: update on patient enrollment

Company: Celyad (Belgium)

Product: CYAD-01 - NKR-2 (NKG2D CAR T-Cell)

Action mechanism:

  • cell therapy/immunotherapy product/gene therapy/CAR-T cell therapy. NKG2D CAR T-Cell is an autologous chimeric antigen receptor T lymphocyte (CAR T-cell) therapy constructed using the native sequence of non-engineered natural killer cell (NK cell) receptors which, unlike traditional CAR technologies such as those targeting the CD19 antigen, have the potential to target a broad range of solid tumors and blood cancers by targeting ligands present on numerous cancer types. NKG2D CAR T-Cell could be also a potential new treatment option for patients with solid tumors such as breast, colorectal, lung, liver, ovarian and bladder cancer. The research underlying this technology was originally conducted at Dartmouth College by Professor Charles Sentman, and has been published in numerous peer-reviewed publications such as Journal of Immunology, Cancer Research and Blood.
 

Disease: colorectal cancer, ovarian Cancer, urothelial carcinoma, triple-negative breast cancer, pancreatic cancer, acute myeloid leukemia/myelodysplastic syndrome, multiple myeloma

Therapeutic area: Cancer - Oncology

Country: Belgium, USA

Trial details:

  • THINK (THerapeutic Immunotherapy with NKR-2) is a multinational open-label Phase Ib study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 T-cells in seven, refractory cancers including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma). The trial will test three dose levels adjusted to body weight: up to 3x108, 1x109 and 3x109 CAR-T NKR-2 cells. At each dose, the patients will receive three successive administrations, two weeks apart, of CAR-T NKR-2 cells. The dose escalation part of the study will enroll up to 24 patients while the extension phase would enroll 86 additional patients.
  • The seven indications evaluated in the THINK trial were selected based on evidence generated in the pre-clinical settings and in the first study recently completed (a Phase I single injection, dose escalation study evaluating NKR-2 T-cells in 12 patients suffering from Acute Myeloid Leukemia (AML) or Multiple Myeloma (MM) at Dana Farber Cancer Institute in Boston, MA, USA). (NCT03018405)

Latest news:

  • • On June 19, 2017, Celyad announced early clinical results at the 3-month follow-up of the first dose-level in the solid tumor arm of the THINK trial (THerapeutic Immunotherapy with CAR-T NKR-2). At the first 3x108 cell dose-level administered to a total of three patients with metastatic cancer, the two colorectal cancer (mCRC) patients, who were progressing after at least two prior chemotherapy regimens, achieved a confirmed Stable Disease (SD) according to RECIST criteria at three months. According to recent studies conducted on similar patient populations, median progression free survival in these patients under standard of care is between 1.9 and 3.2 months. The third patient, a refractory pancreatic patient, was in progression at the same time point. No toxicity signals were observed in any of the patients.
  • Patients in the second dose of the solid tumor arm (1x109) are currently being enrolled and treated. The hematological cancer dose escalation arm, including relapsing/refractory acute myeloid leukemia and multiple myeloma patients, is progressing. The first dose patients have been registered and are being treated with no toxicity signals to date.
  •  • On April 28, 2017, Celyad announced the dosing of the first patient of the second dose in the solid tumor arm of its THINK trial. This first ovarian cancer patient has been dosed at Roswell Park Cancer Institute (Buffalo, New York). At the first solid tumor dose-level, one pancreatic and two colorectal cancer patients were successfully dosed. None of these patients experienced dose limiting adverse events.
  • • On March 8, 2017, Celyad announced that the FDA authorized the initiation of the THINK trial in the U.S.
  • • On February 16, 2017, Celyad announced the registration of a first refractory multiple myeloma patient in the THINK trial. This patient is expected to receive the first dose-level (3x108 CAR-T NKR-2 cells) in the coming weeks, opening the first cohort of the hematological arm of the study. Celyad now looks forward to enrolling patients suffering from acute myeloid leukemia or multiple myeloma into the hematological arm of THINK.
  • • On January 11, 2017, Celyad announced the activation of a second clinical site in Belgium for the THINK trial, with the registration of a pancreatic cancer patient at Cliniques Universitaires Saint-Luc.
  • • On January 5, 2017, Celyad announced that the first patient of the THINK trial started cell processing in Belgium. Blood was collected from this patient and first CAR-T NKR-2 dose level infusion (3x108 cells) is expected in January 2017.
  • • On November 21, 2016, Celyad announces the approval in Belgium to initiate the THINK clinical trial. THINK is the second clinical trial of its NKR-2 product candidate, a CAR-T cell therapy using NKG2D ligands as a target, to evaluate safety and efficacy in seven cancer indications including both solid and hematological malignancies.

Is general: Yes