Benzinga | Jun 4, 2021 07:03AM EDT

Fate Therapeutics Reports Interim Data From Phase 1 Study Of FT516 In Combo With Rituximab For B-Cell Lymphoma At American Society Of Clinical Oncology

8 of 11 Patients in Dose Escalation Cohorts 2 and 3 Achieved Objective Response

6 of 11 Patients Achieved Complete Response, including 2 Patients Previously Treated with Autologous CD19 CAR T-cell Therapy

Favorable FT516 Safety Profile Was Observed; No FT516-related Serious Adverse Events or FT516-related Grade 3 or Greater Adverse Events

Outpatient Treatment Regimen Was Well-tolerated; No Events of Any Grade of Cytokine Release Syndrome, Immune Effector Cell-Associated Neurotoxicity Syndrome, or Graft-vs-Host Disease

SAN DIEGO, June 04, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, today highlighted positive interim Phase 1 data from the Company's FT516 program for patients with relapsed / refractory B-cell lymphoma at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting being held virtually June 4-8, 2021. FT516 is the Company's universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The ongoing Phase 1 dose-escalation study of FT516 is currently enrolling patients in the fourth dose cohort of 900 million cells per dose.

As of the data cutoff date of March 11, 2021, four patients in the second dose cohort of 90 million cells per dose and seven patients in the third dose cohort of 300 million cells per dose were evaluable for assessment of safety and efficacy. Eight of eleven patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria (see Table 1). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy.

"These additional data from our Phase 1 study of FT516 administered off-the-shelf in the outpatient setting continue to reinforce its differentiated safety profile and underscore its potential clinical benefit," said Wayne Chu, M.D., Senior Vice President of Clinical Development of Fate Therapeutics. "Based on the favorable therapeutic profile of FT516 that continues to emerge and the potential to treat patients on-demand without delay, we plan to initiate multiple indication-specific, dose-expansion cohorts for patients with B-cell lymphomas to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including those used as standard-of-care in earlier-line settings."

The ongoing Phase 1 clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine), a single-dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting.

Safety Data

No dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no treatment-emergent adverse events (TEAEs) of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were reported by investigators (see Table 2). All Grade 3 or greater TEAEs were consistent with lympho-conditioning chemotherapy and underlying disease. Of note, a Grade 3 or greater TEAE of infection was reported in one patient only. There were no discontinuations due to adverse events, and no patients withdrew from the study except in the setting of disease progression. 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

As of the data cutoff date of March 11, 2021, eleven relapsed / refractory patients in the second and third dose cohorts were evaluable for assessment of safety and efficacy. Of the eleven patients, nine patients completed both FT516 treatment cycles and eight patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria. Notably, two of four patients previously treated with autologous CD19 CAR-T cell therapy achieved a complete response. Two patients showed progressive disease following the first FT516 treatment cycle and discontinued treatment. The Company previously reported that two patients treated in the first dose cohort (30 million cells per dose) showed progressive disease.

FT516 Dose Cohorts 2 (90 million cells / dose) and 3 (300 million cells / dose) Patients No Prior Autologous Prior Autologous CD19 CAR T CD19 CAR Tn 11 7 4Objective Response (%) 8 (73%) 6 (86%) 2 (50%)Complete Response (%) 6 (55%) 4 (57%) 2 (50%)

Patient Case Study

The ASCO presentation featured a case study of a 36-year old male with triple-hit, high-grade B-cell lymphoma with rearrangements of MYC, BCL2, and BCL6 genes. The patient was refractory to all prior lines of therapy with the exception of autologous CD19 CAR T-cell therapy, for which a complete response of two months' duration was achieved. The patient was most recently refractory to an investigational CD20-targeted T-cell engager and presented with bulky lymphadenopathy with the largest lesion measuring approximately 10 centimeters. The first FT516 treatment cycle resulted in a complete response with resolution of all metabolically active disease and 85% reduction in the size of target lesions. Subsequent to the data cutoff date of March 11, 2021, the patient completed a second FT516 treatment cycle after which the response assessment continued to show complete response.

Table 1. Interim Data from FT516 Phase 1 Study in Relapsed / RefractoryB-cell Lymphoma Prior Systemic TherapySubject # Prior Prior Outcome from Most FT516# Lymphoma Type # Prior CD20- CD19 Recent Prior Response1 Regimens Targeted CAR T Therapy RegimensDose Cohort 2 ? 90 million cells / dose2005 DLBCL 3 2 Y Refractory CR2006 DLBCL 2 2 N Relapsed PR2007 DLBCL (DH) 3 3 Y Relapsed PD2012 iNHL 1 1 N Relapsed CRDose Cohort 3 ? 300 million cells / dose2008 FL 6 6 N Relapsed CR2009 DLBCL (DH/DE) 4 3 Y Relapsed PD22010 FL 4 2 N Relapsed CR2011 Transformed 4 2 N Refractory PR iNHL2013 DLBCL3 2 2 N Refractory CR42014 HGBCL 1 1 N Refractory PD22015 HGBCL (TH) 7 5 Y Refractory CR4

As of March 11, 2021 database entry. Data subject to source document verification.

CR = Complete Response; PR = Partial Response; PD = Progressive Disease

CAR = Chimeric antigen receptor; DH/DE = Double-hit / double expressor; DLBCL = Diffuse large B-cell lymphoma; FL = Follicular lymphoma;

Gr = Grade; HGBCL = High-grade B-cell lymphoma; iNHL = Indolent non-Hodgkin lymphoma; TH = Triple-hit; Transformed iNHL = Aggressive B-cell lymphoma transformed from indolent non-Hodgkin lymphoma

1 Cycle 2 Day 29 protocol-defined response assessment per Lugano 2014 criteria

2 Subject did not proceed to Cycle 2

3 Confirmed DLBCL (transformation from Gr3A FL) subsequent to the data cutoff date of March 11, 2021

4 Cycle 2 Day 29 protocol-defined response assessment reported subsequent to the data cutoff date of March 11, 2021

Table 2. TEAEs of Interest from FT516 Phase 1 Study in Relapsed / RefractoryB-cell Lymphoma DL2 = 90M / dose DL3 = 300M / Total 1 FT516- (n=4) dose (n=13) Relatedn (%) (n=7) All Grade All Grade All Grade All Grade 3+ Grade 3+ Grade 3+ GradeCRS - - - - - - -ICANS - - - - - - -GvHD - - - - - - -Infections 2 (50%) 1 (25%) - - 2 (15%) 1 (8%) -FT516-related SAEs - - - - - -

CRS = Cytokine Release Syndrome; DL = Dose Level; GvHD = Graft vs. Host Disease; ICANS = Immune Cell-Associated Neurotoxicity Syndrome;

M = Million; SAE = Serious Adverse Event; TEAE = Treatment-Emergent Adverse Event

1 Includes two subjects in the first dose cohort of 30 million cells per dose

About Fate Therapeutics' iPSC Product Platform

The Company's proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company's first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company's platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics' iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.