Phase 1 Trials of iPSC-Derived Natural Killer Cells Produce Positive Interim Results for Relapsed/Refractory AML

The interim activity and safety data observed were positive for both FT516 and FT538 monotherapy for patients with relapsed or refractory acute myeloid leukemia.

Positive interim data from an ongoing phase 1 dose-escalation study investigating FT516 as monotherapy to treat patients with relapsed or refractory acute myeloid leukemia (AML) were announced by Fate Therapeutics Inc., the company responsible for the off-the-shelf, induced pluripotent stem cell (iPSC)–derived natural killer (NK) cell immunotherapy.

More, a phase 1 dose-escalation trial investigating FT538 as monotherapy is also ongoing, with positive data from the first dose cohort of 3 patients with relapsed or refractory AML reported.

“We are highly encouraged by these phase 1 data in patients with relapsed / refractory AML, which clearly indicate that off-the-shelf, iPSC-derived NK cells administered as monotherapy in the outpatient setting were well-tolerated, and have the potential to induce complete leukemic blast clearance in the bone marrow and confer durable remissions without further therapeutic intervention,” Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics, said in a press release. “Complete leukemic blast clearance in the bone marrow is essential as recent studies in relapsed / refractory AML have shown that this clinical outcome results in a statistically-significant improvement in patient survival.”

The FT516 phase 1 study population is divided into 2 cohorts, with 3 patients in the first and 6 in the second dose cohort. The first dose cohort features 90 million cells per dose while the second dose cohort features 300 million cells per dose.

Of the 9 total patients, 6 experienced anti-leukemic activity evidenced by the reduction in bone marrow blasts. More, of the 4 patients who had a complete response and complete clearance of leukemic blasts in the bone marrow, 3 achieved a best overall response of complete remission with incomplete hematologic recovery (CRi) as defined by the response criteria set forth by the 2017 European LeukemiaNet (ELN).

There were no dose-limiting toxicities observed in this group of patients, with the treatment schedule being well tolerated. The only grade 3 or greater adverse event (AE) observed was grade 3 febrile neutropenia experienced by 3 patients.

The FT516 phase 1 dose-escalation trial is ongoing and currently enrolling patients into a third dose cohort of 900 million cells per dose.

As for the FT538 study, 2 of the 3 patients were evaluable for safety and activity, while 1 patient discontinued treatment after the first treatment cycle because of clinical evidence showing failure to respond to treatment. One of the 2 remaining patients had adverse molecular risk as defined by the 2017 ELN risk category.

There were no dose-limiting toxicities or grade 3 or greater AEs observed in this patient cohort.

“Additionally, we are excited that a patient receiving FT538 in the initial dose-escalation cohort achieved a complete remission with incomplete hematologic recovery, and that FT538 continued to be detected in the peripheral blood at Day 8 post-infusion,” said Wolchko. “This suggests that the additional engineered functionality of FT538 can augment NK cell pharmacokinetics without the need for exogenous cytokine support during patient treatment.”

The data cutoff date for the phase 1 trials was April 16, 2021.

Fate Therapeutics Inc. is a clinical-stage biopharmaceutical company whose iPSC platform allows for off-the-shelf, engineered, homogeneous cell products to be mass produced and administered over multiple doses.


Fate Therapeutics Announces Encouraging Interim Phase 1 Data for iPSC-derived NK Cell Programs in Relapsed / Refractory Acute Myeloid Leukemia. News release. Fate Therapeutics Inc. Published May 13, 2021. Accessed May 18, 2021.