Cell Therapy
Regulatory & Standards

FDA RMAT Designation Granted to Fate Therapeutics for FT516 Treatment of Relapsed/Refractory DLBCL

Anna Osborne
16 December 2021
Fate Therapeutics has reported positive response data for their ongoing Phase I study of the company’s universal allogeneic NK cell product candidate, FT516, as a treatment for relapsed/refractory (r/r) B-cell lymphoma (BCL).  

The clinical-stage biopharmaceutical company additionally announced at the 63rd American Society of Haematology Annual Meeting and Exposition that FT516 has been granted RMAT designation by the FDA, for the treatment of r/r diffuse large B-Cell lymphoma (DLBCL). DLBCL is an aggressive form of lymphoma and also the most common type of BCL in the US. 

“The RMAT designation for the treatment of relapsed / refractory DLBCL reflects the positive clinical data we have observed with FT516 in the dose-escalation stage of our Phase I study” explained Wayne Chu,, Senior Vice President of Clinical Development at Fate Therapeutics.  

FT516 is a cellular immune-oncology therapy derived from a clonal master iPSC line. As a biopharmaceutical company with a dedication towards investigating cellular Immunotherapies as treatments for patients with cancer, Fate Therapeutics use iPSCs to create genetically engineered clonal master cell lines to provide off-the-shelf renewable and cost effective advanced immune-oncology therapies. 

 The FT516 iPSC line has been modified to enhance their NK cell properties, with an engineered high-affinity expression of improved binding non-cleavable CD16 (hnCD16), a Fc receptor. This enhances the antibody-dependent cellular cytotoxicity (ADCC) mechanism by which NK cells recognise, bind and kill cancer cells coated in antibodies.  

The Phase I clinical trial of FT516 in r/r BCL consisted of two cycles of a dose-escalation treatment regime administered in an out-patient setting, consisting of: three weekly doses of FT516 with IL-2 cytokine support, three days’ treatment of conditioning chemotherapy and a single-dose of rituximab. FT516 is designed in order to synergise well with these and other established cancer therapies.  

Results from 18 patients in the study were evaluated. Eight patients with aggressive BCL had experienced previous treatment with autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, three of these achieved an objective and complete response (38%).  

Ten patients were naïve to autologous CD19-targeted CAR T-cell therapy, five of these suffered with aggressive BCL and five with indolent BCL, eight of these achieved an objective response (80%), five of which achieved a complete response (50%).   

At three months all of the eleven patients who showed an objective response still reported an on-going response (61%), and at a median follow-up of 8.3 months eight of these patents reported an on-going response (44%).  

Additional to the promising response data, FT516 was reported to be well tolerated by patients with no treatment-emergent adverse events. There were also no observations of anti-product T- or B-cell mediated host-versus-product alloreactivity. Non-evident dose-limiting toxicities creates great potential for the administration of up to six doses of FT516 in out-patient environments, before patient matching is required, saving crucial time and reducing expense.  

The preliminary clinical evidence from the Phase I FT516 trial so far suggests that this therapeutic could be used as a potential treatment for the serious and potentially life-threatening condition r/r DLBCL.  

Going forward, enrolment into a dose-expansion stage of the Phase I FT516 trial involving three disease-specific cohorts, has been initiated. This phase will see 900 million cells per dose of FT516 administrated alongside rituximab and conditioning chemotherapy. Plans are also in place for the enrolment of an expansion cohort of FT516 without conditioning chemotherapy. This should provide investigational hope for FT516 to achieve it’s “potential to deliver deep and durable responses for patients with advanced B-cell lymphomas,” concluded Wayne Chu. 

Source:  Fate Therapeutics press release