A Phase 1 trial evaluating Celyad’s CYAD-101 — a donor-derived CAR T-cell product — to treat metastatic colorectal cancer has dosed its first patient, the company announced.
The trial, called Allo-SHRINK (NCT03692429), is testing the treatment, in combination with standard chemotherapy, in patients whose tumors cannot be removed with surgery.
“The initiation of the alloSHRINK trial marks a critical milestone for our organization,” Christian Homsy, CEO of Celyad, said in a press release. “CYAD-101 represents a potential first-in-class approach to allogeneic [donor-derived] CAR-T therapy.”
Traditionally, CAR T-cell therapies consist of a patient’s own immune cells, which are harvested and modified in the lab to recognize cancer cells. These cells are then expanded to several million, and injected back into the patient so they can fight the tumor.
But while autologous (patient-derived) CAR T-cell therapies have shown promise in multiple cancer types, researchers aren’t always able to collect enough cells from a patient to create the treatment.
Celyad developed CYAD-101 to be an allogeneic CAR T-cell therapy where the immune cells are collected from healthy donors, rather than the patient.
Cells in CYAD-01 produce a chimeric receptor — called NKG2D — that recognizes multiple tumor proteins, extending its potential usefulness to several cancers.
Since the cells used in CYAD-101 come from genetically different individuals, they are also engineered to carry a molecule — the inhibitory peptide TIM — that prevents the patients’ immune system from recognizing them as foreign.
Allo-SHRINK is an open-label study (no placebo group) aiming to recruit 36 patients at clinical sites in Belgium and United Kingdom; enrollment information is available here. The study has two phases, a dose-escalation stage followed by a dose-expansion phase.
First, the study will evaluate the efficacy and safety of escalating CYAD-101 doses — 100 million, 300 million and 1 billion cells per injection — together with FOLFOX chemotherapy (folinic acid, fluorouracil, and oxaliplatin).
Patients will be given six cycles of chemotherapy, given every two weeks. CYAD-101 will be given in three injections, within the third, fourth, and fifth chemotherapy cycles. In this part, researchers aim to determine the treatment’s safety and to identify the best CYAD-101 dose for further testing.
In its second stage, a larger group of patients will receive CYAD-101 at the recommended dose, to continue studying its safety and efficacy.
“CYAD-101 represents Celyad’s second oncology program to enter the clinic for the treatment of metastatic colorectal cancer and balances the company’s autologous clinical candidate CYAD-01, which has demonstrated encouraging preliminary results in the Phase 1 SHRINK trial,” said Frédéric Lehmann, vice president of Clinical Development & Medical Affairs at Celyad.
“We believe investigating CYAD-101 in the alloSHRINK trial will leverage our clinical experience to date in the treatment of metastatic colorectal cancer as we look to develop novel therapies for this devastating disease,” he added.
Primary data collection in the alloSHRINK study is expected to finish in November 2020.
While CYAD-101 is derived from healthy volunteers, the company also has a traditional CAR T-cell product derived from patient’s own immune cells. This product, called CYAD-01, provided the basis for CYAD-101 development.
CYAD-01 is currently being evaluated in two Phase 1 trials for colorectal cancer patients whose disease has spread to the liver. The SHRINK (NCT03310008) trial is for patients whose liver metastasis may be removed by surgery (possibly resectable), and the LINK study (NCT03370198) is for those whose liver metastases are inoperable.
CYAD-01 is also being evaluated in a third trial (NCT03018405) in patients with seven types of refractory (treatment resistant) cancers, including five solid tumors — colorectal, ovarian, bladder, triple-negative breast, and pancreatic cancers — and two blood cancers, acute myeloid leukemia and multiple myeloma.