FDA OKs Phase 1 Trial to Test Celyad’s Donor-derived CAR T-cell Therapy in Colorectal Cancer

FDA OKs Phase 1 Trial to Test Celyad’s Donor-derived CAR T-cell Therapy in Colorectal Cancer

Celyad will soon begin clinical development of its immunotherapy CYAD-101 (CAR-T NKG2D) and evaluate its potential as a treatment for patients with colorectal cancer that cannot be surgically removed.

The first-in-human Phase 1 trial, called Allo-SHRINK, comes after the approval of an investigational new drug application for CYAD-101 by the U.S. Food and Drug Administration.

Traditionally, CAR T-cell therapies consist of the collection of a patient’s own immune cells, which are modified in the lab to recognize cancer cells, expanded, and injected back into the patient.

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.

This led Celyad to develop CYAD-101, which is an allogeneic CAR T-cell therapy, meaning immune cells are collected from healthy donors, rather than the patient.

CYAD-101 is based on features of CYAD-01, an investigational autologous CAR T-cell treatment also being developed by Celyad. Cells in CYAD-01 produce a chimeric receptor — called NKG2D — that recognizes multiple tumor proteins, a promising approach for nearly 80 percent of all cancers.

Because it is derived from genetically different individuals, cells in CYAD-101 also carry a molecule that prevents the patients’ immune system from recognizing them as foreign.

“We are pleased to have achieved this important milestone,” Christian Homsy, MD, CEO of Celyad, said in a press release. “Celyad is the first company clinically evaluating a non-gene edited CAR-T candidate, which, we believe, offers significant advantages over gene edited approaches.”

Celyad’s autologous approach, CYAD-01, is being tested in three Phase 1 trials for different cancers.

SHRINK (NCT03310008) is a study testing increasing doses of CYAD-01, given along with chemotherapy, in colorectal cancer patients whose liver metastasis may be removed by surgery.

The LINK study (NCT03370198) is assessing asceding doses of CYAD-01 in colorectal cancer patients with liver metastases that cannot be removed by surgery. The treatment is given alone and injected directly into the liver artery.

A third trial (NCT03018405) is evaluating CYAD-01 in seven types of refractory cancers, including five solid tumors — colorectal, ovarian, bladder, triple-negative breast, and pancreatic cancers — and two blood cancers — acute myeloid leukemia and multiple myeloma.

Preliminary data from SHRINK and LINK showed no treatment-related toxicities in the first patient treated in each trial.

“Our non-gene edited program consists of a family of technologies aimed at reducing or eliminating T cell receptor (TCR) signaling without requiring genetic manipulation,” Homsy said. “CYAD-101 is part of a robust clinical development plan, establishing the foundations of next generation CAR-T products.”