Off-the-shelf natural killer cell therapies induce response in advanced B-cell lymphoma
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Most patients who received one of two investigational natural killer cell therapy regimens for relapsed or refractory B-cell lymphoma achieved complete response, according to topline data released by the agents’ manufacturer.
An ongoing phase 1 dose-escalation study is evaluating FT596 (Fate Therapeutics), a gene-edited allogeneic induced pluripotent stem cell (IPSC)-derived natural killer (NK) cell therapy.
The agent is engineered to include a CD19-directed chimeric antigen receptor, a high-affinity 158V, noncleavable CD16 fragment chain receptor and an IL-15 receptor fusion that promotes enhanced NK cell activity.
All study participants received preconditioning chemotherapy with 500 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine 3 days before cell therapy infusion. They then received FT596 as monotherapy or in combination with a single dose of 375 mg/m2 rituximab (Rituxan; Genentech, Biogen).
Ten (71%) of the 14 patients who received the highest two dose levels (90 million cells or 300 million cells) achieved objective response. Seven patients (50%) achieved complete response to therapy by day 29 after FT596 infusion as determined by PET/CT using Lugano 2014 criteria.
Researchers observed no dose-limiting toxicities or cases of immune effector cell-associated neurotoxicity syndrome (ICANS). They reported one case each of grade 1 and grade 2 cytokine release syndrome; both resolved on the same day as symptom onset, according to a Fate-issued press release.
Fate Therapeutics also reported encouraging results from a phase 1 dose-escalation trial of FT516, a gene-edited, allogeneic IPSC-derived NK cell therapy engineered to include a high-affinity 158V, noncleavable CD16 fragment chain receptor.
The regimen — designed to be administered in the outpatient setting — includes up to two treatment cycles. Each cycle consists of 3 days of preconditioning lymphodepletion with 500 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine, a single dose of 375 mg/m2 rituximab, and three weekly doses of FT516 with IL-2 cytokine support.
Eight of 11 patients (73%) in the second (90 million cells) and third (300 million cells) dose cohorts achieved objective response by day 29 after the second treatment cycle, including six patients (55%) who achieved complete response as confirmed by PET/CT using Lugano criteria.
All eight patients who achieved response to therapy by day 90 after initial infusion of FT516 maintained ongoing responses as of the data cutoff date of July 7.
Researchers reported no dose-limiting toxicities or serious grade 3 or higher treatment-related adverse events among patients who received the FT516 regimen, including no reports of ICANS, CRS or graft-versus-host disease.
“We are very pleased with the interim safety, response rates and durability of responses observed in our ongoing clinical studies of FT516 and FT596 for the treatment of patients with relapsed [or] refractory B-cell lymphomas,” Scott Wolchko, president and CEO of Fate Therapeutics, said in the release. “These data continue to demonstrate that our off-the-shelf, iPSC-derived NK cell product candidates can uniquely deliver substantial therapeutic benefit and expand patient access to cell-based cancer immunotherapies.”
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