Fate Therapeutics Highlights Positive Interim Data from its Phase 1 Study of FT516 in Combination with Rituximab for B-cell Lymphoma at 2021 ASCO Annual Meeting
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
As of the data cutoff date of
“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
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.
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.
As of the data cutoff date of
|FT516 Dose Cohorts 2 (90 million cells / dose) and 3 (300 million cells / dose)|
|Patients||No Prior Autologous
CD19 CAR T
CD19 CAR T
|Objective 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
|Table 1. Interim Data from FT516 Phase 1 Study in Relapsed / Refractory B-cell Lymphoma|
||Prior Systemic Therapy||FT516
|# Prior CD20-
|Outcome from Most
Recent Prior Therapy
|Dose Cohort 2 – 90 million cells / dose
|Dose Cohort 3 – 300 million cells / dose|
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
4 Cycle 2 Day 29 protocol-defined response assessment reported subsequent to the data cutoff date of
|Table 2. TEAEs of Interest from FT516 Phase 1 Study in Relapsed / Refractory B-cell Lymphoma|
||DL2 = 90M / dose
|DL3 = 300M / dose
|All Grade||Grade 3+||All Grade||Grade 3+||All Grade||Grade 3+||All Grade|
|Infections||2 (50%)||1 (25%)||-||-||2 (15%)||1 (8%)||-|
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.
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Scientists from the Company have shown in a peer-reviewed publication (Blood. 2020;135(6):399-410) that hnCD16 iPSC-derived NK cells, compared to peripheral blood NK cells, elicit a more durable anti-tumor response and extend survival in combination with anti-CD20 monoclonal antibodies in an in vivo xenograft mouse model of human lymphoma. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the safety and therapeutic potential of the Company’s iPSC-derived NK cell product candidates, including FT516, its ongoing and planned clinical studies, and the expected clinical development plans for FT516. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in studies of its product candidates, including preclinical studies and clinical trials of any of its product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that the Company may cease or delay clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying the Company’s product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the
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Source: Fate Therapeutics, Inc.