Clinical Trials

Date: 2016-12-07

Type of information: Presentation of results at a congress

phase: 1-2a

Announcement: presentation of results at the 58th American Society of Hematology (ASH) Annual Meeting

Company: Celyad previously known as Cardio3 Biosciences (Belgium)

Product: 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: acute myeloid leukemia, multiple myeloma

Therapeutic area: Cancer - Oncology

Country:

Trial details:

• The CAR-T NKR-2 Phase I trial is a single infusion, dose escalation study evaluating the safety and feasibility of NKR-2 CAR-T cells in AML and MM patients. 12 patients were treated at low escalating doses NKR-2 cells (max 3x10⁷). This study was completed in September 2016 with a successful safety follow-up for all dose level cohorts.

Latest news:

• • On December 7, 2016, Celyad presented new data from the Phase I trial of NKR-2 in patients with acute myeloid leukemia  and multiple myeloma at the 2016 American Society of Hematology (ASH) Annual Meeting  in San Diego. Data presented demonstrate the drug to be safe and well tolerated in the highest dose level tested to date (3x10⁷) as well as showing early efficacy signals, including prolonged survival. Highlights of the data include: strong safety signals, including no cases of cytokine release syndrome, cell-related neurotoxicity, auto-immunity, or CAR-T related death. Although no blast reduction was observed, an AML patient reported no progression (3+months) and improvement in all hematological parameters under no additional therapy at the highest dose (3x10⁷). Other previously reported patients also showed prolonged survival with unanticipated responses to subsequent treatments, and improvements in hematological parameters despite aggressiveness of baseline disease. In vitro testing of the two patients for which tumor samples were available showed that CAR-T NKR-2 destroyed tumor cells, confirming the relevance of the previously published pre-clinical work.
• • On July 14, 2016, Celyad announced the successful completion of the 21-day safety follow-up of the first patient enrolled at the fourth dose level in its Phase I/IIa clinical trial evaluating the safety and feasibility of its NKR-2 T-cell therapy using Tcells engineered to express the NKG2D receptor in acute myeloid leukemia and multiple myeloma patients. No safety issues ortoxicities were reported.
• • On January 5, 2016, Celyad announced the completion of the 30-day safety follow-up of the first patient enrolled in the second cohort in the Phase I clinical trial evaluating the safety and feasibility of its NKG2D CAR T-cell therapy, in cancer patients suffering from acute myeloid leukemia  or multiple myeloma. The Phase I/IIa trial is designed to assess the safety and feasibility of NKG2D CAR T-Cells, with secondary endpoints including clinical activity in two different haematological indications. Data readouts from the first 12 patients treated in the Phase I portion are expected in mid-2016. Once the recommended dose is determined, the IIa phase of the trial will enroll 12 additional patients.
• • On December 1, 2015, Celyad announced the infusion of the first patient of the second cohort of its Phase I clinical trial evaluating NKG2D CAR T-Cell therapy in acute myeloid leukaemia  and multiple myeloma  indications. Data readouts from the first 12 patients treated in the Phase I portion are expected in mid-2016. Once the recommended dose is determined, the IIa phase of the trial will commence, with 12 additional patients treated at the recommended dose.
• • On November 10, 2015, Celyad announced the completion of the 30-day safety follow-up of the final patient enrolled in the first cohort of the Phase I clinical trial evaluating the safety and feasibility of its NKG2D CAR T-Cell therapy, in cancer patients suffering from acute myeloid leukemia or multiple myeloma. This Phase I trial aims to assess the infusion of four escalating doses of NKG2D CAR T-Cells in four consecutive patients cohorts of three patients each. Following infusion of the first dose of NKG2D CAR T-cells to the three patients of the first cohort (2 AML and 1 MM), no treatment related safety issues were reported with the treatment over the follow-up period of 30 days. The full data readout from the Phase I trial focusing on 12 patients is expected in mid-2016. The trial is designed to assess the safety and feasibility of NKG2D CAR T-Cell as primary endpoints, with secondary endpoints including clinical efficacy.
• • On June 11, 2015, Celyad announced the completion of the 30-day safety follow-up of the first patient enrolled in the  Phase I clinical trial evaluating the safety and feasibility of its NKG2D CAR T-cell therapy, in cancer patients suffering from acute myeloid leukemia or multiple myeloma. The first patient suffers from acute myeloid leukemia. This Phase I trial is a dose escalating study. Following the infusion of the first dose of NKG2D CAR T-cell, no safety issues were reported with the treatment over the follow-up period of 30 days. This triggers the enrollment of the next two patients in the first dose cohort.
• • On April 20, 2015, Cardio3 BioSciences, soon to be renamed Celyad, announced the infusion of the first patient enrolled in the Phase I clinical trial evaluating the safety and feasibility of its NKG2D CAR T-cell therapy, in cancer patients suffering from acute myeloid leukemia  or multiple myeloma. This Phase I trial is a dose escalating study. Following the infusion of the first dose of NKG2D CAR Tcell, there were no short term adverse events observed in that patient. A pre-defined, staggered enrolment of two additional patients at the same dose level is expected to occur after an additional 30-day safety assessment of the first infused patient. This dose-escalation trial is expected to enrol a total of approximately 24 patients and the trial is anticipated to be completed in mid-2016.
• • On April 13, 2015, Cardio3 BioSciences announced the enrollment of the first patient in a Phase I clinical trial evaluating its CAR T-Cell therapy, NKG2D CAR T-Cell, in blood cancer patients with acute myeloid leukemia  or multiple myeloma. Cell engineering and processing will be followed in the coming days by the infusion of NKG2D CAR T-Cells into the patients. NKG2D CAR T-Cell received an Investigational New Drug (IND) clearance, under the name CM-CS1, from the FDA in July 2014 for the Phase I clinical trial in hematologic cancers. This trial is assessing the safety and feasibility of NKG2D CAR T-Cell as primary endpoints, with secondary endpoints including clinical efficacy. Cardio3 BioSciences expects to complete the study in mid-2016 and will provide updates as the trial advances.

 

Is general: Yes