Donor-derived CAR T-cell Therapy ALLO-715 Enters Clinical Testing for Multiple Myeloma

Allogene Therapeutics is launching the first clinical trial testing ALLO-715, its “off-the-shelf” CAR T-cell therapy, for people with multiple myeloma who failed prior therapies.

This follows the recent approval by the U.S. Food and Drug Administration of an investigational new drug (IND) application for ALLO-715. The trial is expected to start in the second half of 2019.

CAR-T cell therapy is a type of immunotherapy in which researchers collect a person’s T-cells — immune cells with anti-cancer activity — and re-engineer them in the lab so they can recognize and eliminate cancer cells. The treated cells are then inserted back into the patient’s body to fight tumors.

Allogene’s ALLO-715 is a kind of CAR T-cell product meant to recognize and eliminate cancer cells containing the B-cell mature antigen (BCMA) protein. But instead of collecting T-cells from patients, researchers harvest them from healthy donors, allowing the therapy to be offered off-the-shelf, or not specially made.

While this allows patients to receive the treatment much faster, a donor-derived product raises the problem of graft-versus-host disease (GvHD). This is a serious complication in which the transplanted T-cells from the healthy donors start attacking the host’s body.

Thus, researchers engineered ALLO-715’s cells to attack only BCMA-positive cells — and included a safety switch, which allowed them to destroy the engineered cells in the presence of Rituxan (rituximab), if needed.

In mouse models of multiple myeloma, treatment with ALLO-715 triggered a strong and durable anti-tumor response. Moreover, the therapy’s anti-tumor activity was maintained after large-scale manufacturing, supporting its potential for multiple myeloma.

Now, the UNIVERSAL Phase 1 trial will test ALLO-715 in people with multiple myeloma who failed to respond to treatment (refractory), or whose cancer progressed after first responding to prior therapy (relapsed).

Before receiving the CAR T-cells, the participants will first be treated with a lymphodepletion regimen. This is meant to eliminate traces of cancer cells, and create room for the newly-injected cells to expand. The regimen will include the company’s anti-CD52 antibody ALLO-647.

“We are very pleased to have received clearance for our second IND this year and look forward to initiating the UNIVERSAL trial in 2019,” David Chang, MD, PhD, president, CEO, and co-founder of Allogene, said in a press release. “We believe an ‘off-the-shelf’ CAR T cell therapy could be game-changing for patients.”

Allogene also is conducting the ALPHA Phase 1/2 trial (NCT03939026) testing another off-the-shelf CAR T-cell therapy, ALLO-501. That treatment is designed for people with diffuse large B-cell lymphoma or follicular lymphoma, the two most common non-Hodgkin’s lymphoma subtypes.