Fate Therapeutics Announces Clinical Data from Landmark Phase 1 Studies of First-ever Universal, Off-the-shelf, iPSC-derived NK Cell Cancer Immunotherapy Programs - Seite 2

FT500 is the first iPSC-derived cell product candidate to emerge from the Company’s iPSC product platform. The FT500 study is an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors. The dose-escalation stage of the study is designed to assess the safety and tolerability of three once-weekly doses of FT500, without IL-2 cytokine support, as a monotherapy and in combination with one of three FDA-approved immune checkpoint inhibitor (ICI) therapies in patients that have failed prior ICI therapy.

As of a November 28, 2019 data cutoff, 12 patients (n=8 monotherapy; n=4 in combination with ICI) have been treated with FT500, and the key clinical findings include:

• Safety. No DLTs, FT500-related SAEs or FT500-related Grade ≥3 AEs, and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, have been reported in 12 patients.
• Tolerability. All 12 patients completed the first FT500 treatment cycle of three once-weekly doses. Nine of 11 patients initiated a second FT500 treatment cycle, with eight of nine patients having completed the second FT500 treatment cycle. One patient is currently pending initiation of a second FT500 treatment cycle. The multi-dose, two-cycle treatment schedule was well-tolerated, and no treatment discontinuations were due to AEs.
• Anti-FT500 T-cell Mediated Immunogenicity. The T-cell compartment of nine patients was evaluated for T-cell mediated host-versus-product allo-reactivity. A TCR repertoire analysis conducted at multiple time points following treatment with FT500 demonstrated that a maximum of up to 6% of the T-cell clones in the patients’ reconstituted T-cell compartment were comprised of pre-existing low-frequency T-cell clones, suggesting that a robust T-cell response against FT500 was not evident. As a point of contrast, in subjects undergoing immunization for infectious disease, it is observed that almost 90% of the T-cell clones that emerge existed in low frequency prior to immunization.
• Anti-FT500 B-cell Mediated Immunogenicity. The antibody repertoire of 11 patients was analyzed for targeting of the six HLA class I types expressed by FT500 to assess B-cell mediated host-versus-product allo-reactivity. Among the 11 patients, a single FT500 anti-HLA antibody with a mean fluorescence intensity (MFI) level of ≥ 5,000 was detected in a single patient, suggesting that a robust anti-FT500 B-cell response was not evident. As a point of reference, in patients undergoing haplo-identical hematopoietic stem cell transplant, an MFI level ≥ 5,000 has been correlated with a 5-fold increase in risk of graft rejection.
• FT500 Anti-tumor Activity. In the monotherapy arm, two of three patients in the 100 million cells per dose cohort and two of five patients in the 300 million cells per dose cohort achieved a best overall response of stable disease per iRECIST. In the ICI combination arm, two of three patients in the 100 million cells per dose cohort achieved a best overall response of stable disease per iRECIST. A fourth patient in the ICI combination arm is currently undergoing treatment in the 300 million cells per dose cohort.

Upon successful completion of the 300 million cells per dose cohort in the ICI combination arm, the Company plans to amend the current FT500 clinical protocol to include IL-2 cytokine support with each dose of FT500 and enrich for cancers that are expected to be amenable to NK cell anti-tumor activity. In the dose-expansion stage of the FT500 Phase 1 study, FT500 will be administered at 300 million cells per dose in combination with ICI therapy under this revised clinical protocol.