Fate's closely watched stem cell-derived NK program raises red flag over durability of response
At the cutting edge of oncology research, biotechs like Fate Therapeutics are looking for ways to craft next-gen cell therapies without relying on patients’ own cells. An early peek at the company’s clinical data looks promising, but will iffy durability results prove a roadblock?
Fate on Thursday revealed an early cut of Phase I data for its FT596 and FT516 induced pluripotent stem cell-derived natural killer cell programs that revealed potential red flags on one of the therapies’ durability over time.
At a three-month check in, eight of 11 B cell lymphoma patients who received FT516, off-the-shelf NK cells engineered with a “non-cleavable” CD16 Fc receptor, reported an objective response with no major safety signals. But at a July 7 cutoff, just five patients (45%) maintained those responses, with two complete responders seeing their disease progress and a partial responder forced to receive an “additional anti-cancer therapy,” Fate said.
It’s a troubling sign for FT516’s durability but not a death knell for the program. The therapy’s safety profile, for instance, with no FT516-linked serious side effects and no FT516-related Grade 3 events or higher, should warm investors’ hearts somewhat. But immediately following the news, shares of $FATE sunk around 10% after the bell, potentially underscoring shareholders’ worries about the drug’s ability to maintain effect.
On a call with analysts Thursday, the Fate team fielded questions on FT516’s durability, particularly compared to results from CD19 CAR-T therapies.
“It’s too early to know ultimately what the long term durability of FT516 is and how that compares to CAR-T therapy,” CEO Scott Wolchko said. “We’re very encouraged by the durability we’ve seen as we follow these patients.”
Fate is one of a group of biotechs leaning on the possibility of engineering donor stem cells to create powerful tumor fighters. NK cells, which are associated with a lower risk of cytokine release syndrome than T cell therapies, hold promise as an option for late-stage cancer patients, many of whom have previously failed on prior immunotherapies and/or cell therapies.
The Phase I study for FT516 dosed the therapy across cohorts up to two treatment cycles including a regimen of three days of conditional chemotherapy followed by a single dose of Roche’s Rituxan and three weekly doses of varying strength of FT516 and IL-2 cytokine support. Patients had received a median of three prior lines of therapy and a median of two prior lines of CD20-targeted therapy. Of the 11 patients in the study, eight had aggressive B cell lymphoma, five patients didn’t respond to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy.
FT516’s results in patients with prior CD19 CAR-T therapy — two of four posted a complete response — spurred Fate to announce a dose-expansion cohort in that population, which the biotech thinks could address a growing market need.
Meanwhile, FT596 posted early data of its own showing promising efficacy. The therapy uses the same platform as FT516 with an additional CAR construct engineered onto the cells in an attempt to address heterogeneous tumor types and antigen escape.
Interim data showed 10 of 14 patients across two dose-escalation cohorts posted an objective response, including seven complete responders, including two of three patients who were treated with a combo of FT596 and Rituxan after autologous CD19 CAR-T therapy.
Fate expects to present further data from both studies at the upcoming ASH conference in December, including a first look at durability of response for FT596.