FDA Grants NK Cell Therapy Fast Track Designation for Recurrent GBM

Robert J. Hariri, MD, PhD

The FDA has granted CYNK-001, a natural killer (NK) cell therapy, with a fast track designation for the treatment of adult patients with recurrent glioblastoma multiforme (GBM), according to a press release from developer Celularity.¹ 

“This designation marks a meaningful milestone for Celularity and validates the potential of our approach to change the cell therapy landscape and improve the lives of patients with GBM and beyond,” said Robert J. Hariri, MD, PhD, founder, chairperson, and CEO of Celularity.

CYNK-001 is a non-genetically modified cryopreserved allogeneic placental hematopoietic stem cell-derived NK cell therapy that is being investigated as an off-the-shelf therapy for the treatment of patients with acute myeloid leukemia, multiple myeloma, GBM, and COVID-19. In preclinical studies, CYNK-001 demonstrated cell killing activity in vitro in leukemia, multiple myeloma, GBM, and SARS-CoV-2–infected cells and is expected to augment the body’s natural immune response in humans.²

In like with NK cell ability, CYNK-001 has cytolytic activity and secretes immunomodulatory cytokines, including IFN-γ, when around tumor cells. CD34-positive CYNK-001 NK cells also express NKG2D and CD94 and the activating receptors DNAM1, NKp30, NKp46, and NKp44.

“We believe the unique attributes of placental-derived cell therapies will allow us to not only overcome the challenges of NK cell proliferation and persistence, but also improve therapeutic availability as compared to adult bone marrow or peripheral blood approaches. We look forward to working more closely with the FDA to advance our clinical trials and, ultimately, to bringing a new potential treatment option to patients suffering from this historically challenging disease,” Hariri added.

CYNK-001 is being explored in a phase 1 study (CYNK001GBM01; NCT04489420) in adult patients with recurrent GBM, which is currently recruiting patients. The study is looking to determine the maximum tolerated dose for CYNK-001.

Patients will be enrolled into either the intravenous administration cohort or a intratumoral administration cohort. In the intravenous group, lymphodepleting chemotherapy will be followed by infusion of CYNK-001 cells. Doses in the intravenous cohort will start at 1.2 x 10⁹ cells/dose and 200 x 10⁶ cells/dose (±50 x 106) in the intratumoral group.

A planned 36 patients are expected to be enrolled who have a Karnofsky performance status score ≥60, adequate organ function, and measurable disease. Those with HIV/AIDs are eligible if they have not had any infections in the past year and those with chronic or a history of Hepatitis C virus infection are allowed in the study if they have a viral load below the limit of quantification, are on viral suppressive therapy, are on concurrent treatment, or have completed curative antiviral treatment.

Anyone who has had recent radiation therapy, growth factor support, chemotherapy, or any prior cellular or gene therapy are excluded form the study. Those with a history of malignancy other than GBM, active autoimmune disease, or immunodeficiency are also unable to join this trial.

The primary end points of the trial are dose-limiting toxicities and adverse events and secondary end points include overall response rate, duration of response, progression-free survival, time to progression, and overall survival.

_References

_{1. Celularity Announces Fast Track Designation by the FDA for our Natural Killer Cell Therapy CYNK-001 in the Treatment of Recurrent Glioblastoma Multiforme. News release. Celularity. March 18, 2021. Accessed March 18, 2021. https://bit.ly/3lpPhyg}

_{2. NK Cell Program. Celularity website. Accessed March 18, 2021. https://celularity.com/nk-cell-platform/}