Clinical-stage biopharmaceutical company Celyad, focusing on the development of CAR-T cell therapies, will be presenting clinical data discussing the company’s pipeline candidates at the upcoming 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) being held November 6-10, 2019, in Washington, D.C.
“SITC 2019 remains an important avenue for us to provide updated results of our clinical programs in metastatic colorectal cancer, and in particular, data from the industry’s first trial investigating an ‘off-the-shelf,’ non-gene edited allogeneic CAR-T candidate for the treatment of solid tumors,” commented Frédéric Lehmann, MD, Vice President of Clinical Development & Medical Affairs at Celyad.
“In addition, disclosing clinical and scientific data from the SHRINK and alloSHRINK dose-escalation Phase I clinical trials in parallel will allow the comparison of results obtained with an autologous CAR-T and its equivalent allogeneic version. As such, this comparison highlights our efforts to understand analytical development in CAR-T space and our ongoing mission to get this much-needed therapy to people living with this deadly cancer, for which there are few treatment options,” Lehmann added.
SHRINK and alloSHRINK Trials
The data to be presented are results from two clinical trials, called SHRINK and alloSHRINK.
The SHRINK study is an open-label, dose-escalation Phase I trial assessing the safety and activity of CYAD-01 administered concurrently with FOLFOX chemotherapy in patients with metastatic colorectal cancer (mCRC). In this trial, patients receive six cycles of FOLFOX (a combination of 5-fluorouracil, leucovorin and oxaliplatin) chemotherapy every two weeks and three administrations of CYAD-01 every two weeks.
CYAD-01 is an investigational CAR-T therapy in which a patient’s T-cells are engineered to express the chimeric antigen receptor (CAR) NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands expressed on tumor cells. In addition to the SHRINK study, the drug is currently in clinical development through a number of trials for hematological malignancies and solid tumors.
The alloSHRINK study is an open-label, dose-escalation Phase I clinical trial assessing the safety and clinical activity of CYAD-101 administered concurrently with FOLFOX chemotherapy in patients with refractory mCRC. Similar to the SHRINK trial for CYAD-01, participating patients receive six cycles of FOLFOX chemotherapy every two weeks and three administrations of CYAD-101 every two weeks.
CYAD-101 is an investigational, non-gene edited, allogeneic or donor derived CAR-T therapy that co-expresses the chimeric antigen receptor (CAR) NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands expressed on tumor cells and the novel inhibitory peptide TIM (T cell receptor [TCR] Inhibiting Molecule). TCR signaling is responsible for Graft versus Host Disease (GvHD), potentially serious complication of allogeneic stem cell transplantation. The complication may occur when donor’s T cells (the graft) consider a patient’s healthy cells (the host) as foreign, and, as a result, attack and damage them. The disease can be mild, moderate or severe. However, in some cases, GvHD can be life-threatening. The expression of TIM reduces signaling of the TCR complex and, as a result, may reduce or eliminate GvHD in patients treated with CYAD-101.
The investigational agent represents a potential first-in-class approach to allogeneic CAR-T therapy.
|P147||Effect of chemotherapy on cellular kinetics of NKG2D-based CAR T-cells in metastatic colorectal cancer patients.||November 8, 2019|
7:00 am. – 8:00 p.m.
|P330||Results from the completed dose-escalation of the alloSHRINK phase I study evaluating the allogeneic NKG2D-based CAR T-cell therapy CYAD-101 in metastatic colorectal cancer patients||November 9, 2019|
7:00 am. – 8:30 p.m.
|P331||Results from the completed dose-escalation phase I SHRINK study evaluating the autologous NKG2D-based CAR T-cell therapy CYAD-01 in metastatic colorectal cancer patients||November 8, 2019|
7:00 am. – 8:00 p.m.
Dose Escalation and Dose Expansion Phase I Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2 Administered Concurrently With FOLFOX in Colorectal Cancer With Potentially Resectable Liver Metastases (SHRINK) – NCT03310008
alloSHRINK – Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells (alloSHRINK) – NCT03692429