On May 13, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, reported encouraging interim Phase 1 data from the Company’s off-the-shelf, iPSC-derived natural killer (NK) cell programs in relapsed / refractory acute myeloid leukemia (AML) (Press release, Fate Therapeutics, MAY 13, 2021, View Source [SID1234579910]). The ongoing Phase 1 dose-escalation study of FT516 as monotherapy is currently enrolling patients in the third dose cohort (900 million cells per dose), with three patients treated in the first dose cohort (90 million cells per dose) and six patients treated in the second dose cohort (300 million cells per dose). The Phase 1 dose-escalation study of FT538 as monotherapy is currently ongoing, with three patients treated in the first dose cohort (100 million cells per dose).
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As of the data cutoff date of April 16, 2021, five of 12 patients had achieved an objective response with complete leukemic blast clearance in the bone marrow (FT516 [n=9]: 3 complete remission with incomplete hematologic recovery [CRi], 1 morphologic leukemia-free state [MLFS]; FT538 [n=3]: 1 CRi). Of the four patients achieving a CRi, one patient successfully proceeded to allogeneic stem cell transplant and the other three patients remained on-study and in remission without further therapeutic intervention, two of whom remained in remission having been on-study for more than six months. Clinical assessments were based on the 2017 European LeukemiaNet (ELN) response criteria (Blood (2017) 129 (4): 424–447).
Importantly, no dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. Patients had received a median of three prior lines of therapy, with 11 of 12 patients refractory to their last prior therapy. At baseline prior to conditioning chemotherapy, 11 of 12 patients had significant hematopoietic impairment, with both neutrophil counts below 1,000/µL and platelet counts below 100,000/µL.
"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. 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," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "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. This suggests that the additional engineered functionality of FT538 can augment NK cell pharmacokinetics without the need for exogenous cytokine support during patient treatment."
FT516 Phase 1 Study
FT516 is an investigational, universal, off-the-shelf NK cell cancer immunotherapy derived from a clonal engineered master induced pluripotent stem cell (iPSC) line. The Phase 1 clinical trial in relapsed / refractory AML is assessing FT516 administered as monotherapy. Up to two cycles of treatment are administered, with each cycle consisting of three days of conditioning chemotherapy followed by three weekly doses of FT516, with IL-2 cytokine support after each FT516 dose. FT516 may be administered in the outpatient setting with no requirement for inpatient monitoring during the treatment period.
Three patients in the first dose cohort of 90 million cells per dose and six patients in the second dose cohort of 300 million cells per dose were assessed for safety and activity (see Table 1). Of the nine patients, eight had adverse molecular risk based on the 2017 ELN risk category and eight patients were refractory to their last prior therapy. Patients had received a median of three prior lines of therapy. At baseline prior to conditioning chemotherapy, all nine patients were significantly cytopenic, with eight patients having neutrophil counts below 1,000/µL and nine patients having platelet counts below 100,000/µL, and the median bone marrow leukemic blast percentage was 39%.
Safety Data
No dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. The multi-dose treatment schedule was well-tolerated with no treatment discontinuations due to adverse events. Three patients experienced Grade 3 febrile neutropenia, and no other FT516-related Grade 3 or greater adverse events were reported by investigators. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without the need for patient matching.
Activity Data
Six of nine relapsed / refractory AML patients showed anti-leukemic activity as evidenced by on-treatment reduction in bone marrow blasts, with four patients achieving an objective response with complete clearance of leukemic blasts in the bone marrow. Three of these four responders achieved a best overall response of CRi based on 2017 ELN response criteria, including two patients in the second dose cohort (Table 1: Subjects 1006 and 1007), each of whom had ongoing remission without further therapeutic intervention at six months’ follow-up, and one patient in the first dose cohort (Table 1: Subject 1001) who successfully proceeded to allogeneic stem cell transplant.
FT538 Phase 1 Study
FT538 is an investigational, universal, off-the-shelf NK cell cancer immunotherapy derived from a clonal master iPSC line engineered with three functional components designed to enhance innate immunity. The Phase 1 clinical trial in relapsed / refractory AML is assessing FT538 administered as monotherapy. Up to two cycles of treatment are administered, with each cycle consisting of three days of conditioning chemotherapy followed by three weekly doses of FT538 without IL-2 cytokine support. FT538 may be administered in the outpatient setting with no requirement for inpatient monitoring during the treatment period.
Three patients were enrolled in the first dose cohort of 100 million cells per dose, two of whom were evaluable for safety and anti-leukemic activity and one patient who discontinued from the study prior to completion of the first treatment cycle due to clinical evidence of failure to respond to therapy (see Table 2). Of the two evaluable patients, one patient had adverse molecular risk based on the 2017 ELN risk category. Both patients had received at least three prior lines of therapy, were refractory to their last prior therapy, and were significantly cytopenic with neutrophil counts below 1,000/µL and platelet counts below 100,000/µL at baseline prior to conditioning chemotherapy.
Safety Data
No dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. The multi-dose treatment schedule was well-tolerated with no FT538-related Grade 3 or greater adverse events reported by investigators. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT538 in the outpatient setting without the need for patient matching.
Activity Data
Both evaluable patients showed anti-leukemic activity as evidenced by on-treatment reduction in bone marrow blasts. One patient (Table 2: Subject 1003), who was refractory to their two most recent prior therapies (an investigational CD33-targeted tri-specific NK cell engager [TriKE], followed by glasdegib in combination with low-dose cytarabine), achieved a CRi based on 2017 ELN response criteria at the end of the first treatment cycle and remained on-study. FT538 was detected in the peripheral blood at Day 8 prior to administration of the second dose in both patients.
CRi (Complete Remission with incomplete hematologic recovery) = Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; recovery of either neutrophils to ≥1,000/µL or platelets to ≥100,000/µL
MLFS (Morphologic Leukemia-free State) = Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; residual neutropenia (<1,000/µL) and residual thrombocytopenia (<100,000/µL)
PD = Progressive Disease
SD = Stable Disease
As of April 16, 2021 database entry. Data subject to source document verification.
a Subject 1001 received 2 of 3 doses of FT538 in the first treatment cycle and discontinued from study due to evidence of non-response to therapy.
Today’s Webcast
The Company will host a live audio webcast today, Thursday, May 13, 2021 at 5:00 p.m. ET to review the relapsed / refractory AML treatment landscape and discuss interim Phase 1 clinical data for the Company’s FT516 and FT538 off-the-shelf, iPSC-derived NK cell programs. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.