FDA Clears Investigational New Drug Application for TCR-NK Cell Therapy in Multiple Myeloma

The FDA has issued a ‘safe to proceed’ for the investigational new drug (IND) application enabling a phase 1 study evaluating NY-ESO-1 TCR/IL-15 NK, a first-in-class engineered T-cell receptor natural killer (TCR-NK) cell therapy for patients with relapsed/refractory multiple myeloma.¹

The phase 1 study, which represents the first TCR-NK trial in hematologic malignancies, is expected to begin in the third quarter of 2023.

The TCR-NK cell therapy is being developed by Syena, a company that was launched by Replay Bio and grounded in research led by Katy Rezvani, MD, PhD, a professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center in Houston. The IND will be sponsored by MD Anderson, and Syena will retain an exclusive licensing agreement for the TCR-NK platform.

"This IND clearance of Syena’s engineered TCR-NK cell technology in hematological malignancies swiftly follows the FDA’s clearance of our solid tumor study in sarcoma, signaling the rapid advancement of our TCR-NK program into the clinic and the breadth of our engineered TCR-NK cell therapy’s potential,” Adrian Woolfson, executive chairman, president, and co-founder of Replay, stated in a news release.

Previously, in June 2023, the FDA granted IND clearance for a study of NY-ESO-1 in patients with synovial sarcoma and myxoid/round cell liposarcoma.2

NY-ESO-1 is an established cancer-testis antigen that creates humoral and cellular immune responses. With re-expression in several cancers and limited expression in healthy tissues, NY-ESO-1 represents a novel target for TCR–T-cell therapy.

NY-ESO-1 TCR/IL-15 NKs are adoptive NK cells that express an affinity-enhanced TCR reactive directed against the NY-ESO-1–specific cord blood–derived NK cells. The cells are designed to express the CD3 and TCR signaling complex and interleukin-15 (IL-15). Moreover, the manufacturing processes are modeled after those for engineered CAR NKs, which have shown safety and efficacy in lymphoma. Prior research has also shown that NY-ESO-1 TCR/IL-15 NK cells do not kill healthy human cell lines derived from organs including the heart, lungs, liver, and kidneys.

“With clinical studies in 2 indications, spanning solid tumors and hematological malignancies, we are excited for the potential of Syena's first-in-class 'off-the-shelf' engineered TCR-NK platform to address multiple unmet clinical needs,” Lachlan MacKinnon, chief executive officer and co-founder of Replay, said.

“NY-ESO-1 is highly expressed in certain patients with multiple myeloma and associated with a poor prognosis, so this clinical study will be key to further understanding the potential of our TCR-NK platform in hematological malignancies,” Katy Rezvani MD, PhD, a professor, director of Translation Research, and section chief in the Department of Stem Cell Transplantation, Division of Cancer Medicine, and the Sally Cooper Murray Endowed Chair in Cancer Research at The University of Texas MD Anderson Cancer Center, added. “I look forward to the study beginning later this year.”

References

1. Replay and MD Anderson announce FDA clearance of IND application for first-in-class T-cell receptor natural killer (TCR-NK) cell therapy for multiple myeloma. News release. Replay Bio. July 24, 2023. Accessed July 26, 2023. https://replay.bio/news/replay-and-md-anderson-announce-fda-clearance-of-ind
2. Replay and MD Anderson announce FDA clearance of IND application for first-in-class T-Cell Receptor Natural Killer (TCR-NK) cell therapy for sarcoma. News release. Replay Bio. June 20, 2023. Accessed July 26, 2023. https://replay.bio/news/replay-and-md-anderson-announce-fda-clearance-of-ind-application