FDA Grants Fast Track Status to CYNK-001 for AML

FDA

The FDA has granted Fast Track Designation to CYNK-001, a non-genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, for the potential treatment of patients with acute myeloid leukemia (AML).¹

“The majority of patients with AML continue to have poor long-term outcomes, particularly those who suffer relapse or have measurable residual disease, necessitating development of novel therapies, including CYNK-001,” Andrew Pecora, MD, president of Celularity, the developer of CYNK-001, said in a press release.

CYNK-001 is a cryopreserved allogeneic off-the-shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells. Celularity noted that the safety and efficacy of CYNK-001 have not yet been established.

In June 2021, it was announced that a phase 1 study (NCT04310592) evaluating CYNK-001 had expanded to include patients with relapsed/refractory AML after a case of conversion to minimal residual disease (MRD) negativity at its highest dose level.² The expansion is in addition to the ongoing trial’s population of patients with MRD-positive disease.

The expansion follows a patient with NPM-1–positive, FLT3-negative AML who had received 5.4 billion CYNK-001 cells, did not experience a dose-limiting toxicity (DLT), and converted from MRD-positive disease to MRD-negative disease upon assessment. The patient also had good-risk cytogenetics.

Following primary induction therapy with 7+3 chemotherapy that failed, the patient received second induction treatment followed by high-dose cytarabine consolidation. The patient experienced a complete clinical response (CR); however, the MRD was persistent and did not clear after 4 months of azacitidine; MRD was confirmed on a marrow biopsy.

The patient then entered on the phase 1 trial and received lymphodepletion before receiving 1.8 billion CYNK-001 cells on days 0, 7, and 14 in the outpatient setting, totaling to 5.4 billion CYNK-001 cells. On day 28, the patient not only had confirmed conversion from MRD-positive to MRD-negative disease, but CYNK-001 cells were present in both the peripheral blood and bone marrow.

In the open-label, multi-dose, phase 1 trial, investigators are evaluating the maximum-tolerated dose (MTD) or maximum-planned dose of CYNK-001 in an estimated 22 patients with AML.³ The estimated completion date of the trial is January 3, 2022.

To be eligible for enrollment, patients must have primary or secondary AML who are in first of second morphological CR, morphological CR with incomplete hematologic recovery, or morphologic leukemia-free state as defined by the European LeukemiaNet recommendations for AML Response Criteria. Additional eligibility criteria include MRD positivity, between the ages of 18 and 80 years old, an ECOG performance status of 2 or lower, and the ability to be off immunosuppressive therapy for at least 3 days prior to CYNK-001 infusion.

Prior central nervous system involvement is permitted if it was treated, and cerebral spinal fluid is clear for at least 2 weeks prior to start of lymphodepletion.

Those who have any significant medical conditions that would prevent them from participating on the trial, laboratory abnormalities, bi-phenotypic acute leukemia, acute promyelocytic leukemia, inadequate organ function, autoimmune disease, and uncontrolled graft-vs-host disease (GVHD) or GVHD requiring corticosteroids, among other factors, were excluded from enrollment.

Patients are administered cyclophosphamide and fludarabine followed by CYNK-001 at 3 varying dose levels on days 0, 7, and 14. The primary end points of the trial are the number of patients who experience a DLT, MTD, and frequency and severity of adverse effects. Secondary outcome measures include the number of patients who convert from MRD positivity to negativity, time to and duration of MRD response, progression-free survival, time to progression, duration of morphologic complete remission, and overall survival.

Celularity has previously stated that it intends to continue dose escalation in the MRD indication to a total 9.0 billion CYNK-001 cells in addition to expanding the study to include those with relapsed/refractory AML.

“We believe that the unique properties of our cell source, including the ability to proliferate and maintain activity, could be the key to improving response rates and durability for patients," Robert Hariri, MD, PhD, founder, chairperson, and chief executive officer of Celularity, said in the press release. "We are pleased to receive this fast-track designation from the FDA for AML supporting continued development of our placental-derived NK cell platform."

CYNK-001 previously was granted Orphan Drug Designation for malignant gliomas and Fast Track Designation for glioblastoma multiforme, Hariri added.

References

1. Celularity Receives Fast Track Designation from U.S. FDA for its NK Cell Therapy CYNK-001 in Development for the Treatment of AML. Celularity. News release. December 27, 2021. Accessed December 27, 2021. https://bit.ly/3euVWEO
2. Celularity announces expansion of human placental hematopoietic stem cell derived natural killer cells (CYNK-001) phase 1 trial in patients with acute myeloid leukemia. News release. Celularity. June 29, 2021. Accessed June 29, 2021.
3. Natural killer cell (CYNK-001) infusions in adults with AML (CYNK001AML01). ClinicalTrials.gov. Updated March 2, 2021. Accessed June 29, 2021. https://clinicaltrials.gov/ct2/show/NCT04310592