The patient was treated at the new fifth dose level and had concomitant metapneumovirus infection.
The FDA has placed Athenex’s autologous GD2 chimeric antigen receptor natural killer T-cell (CAR-NKT) therapy KUR-501 on clinical hold after reports of a patient death in the phase 1 GINAKTI2 study (NCT03294954) assessing the therapy in relapsed/refractory high-risk neuroblastoma (RR HRNB).1
The patient was a young, heavily pretreated man that had been treated at the fifth dose level of 300 million cells/m2 that died around 3 weeks after infusion. The investigational new drug (IND) holder, Baylor College of Medicine (BCM), continues to investigate the death. The patient had human metapneumovirus infection and then a grade 1 cytokine release syndrome (CRS) treated with immunosuppressants. The patient later developed polyclonal hyperleukocytosis complicated by multiorgan dysfunction without evidence of sepsis.
Athenex and BCM are working with the FDA to address the safety concerns and hopefully continue a safe development path for the cell therapy. BCM is considering excluding patients with concomitant viral infections in a new safety risk mitigation plan that may allow the trial to reopen. Athenex stated its hopes that the GINAKIT2 study will be able to reopen in mid-2023 if the FDA lifts its hold. As of now, a safety and preliminary efficacy data update from the trialis planned in the second half of 2023.
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The trial previously reported data in 2022 that included patients treated up to dose level 4 of 100 million cells/m2 of KUR-501.2 The data demonstrated complete expansion of CAR-NKT cells in all treated patients, as well as a tolerable safety profile and some evidence of clinical benefit. Three of 12 participants included in the update responded for a 25% overall response rate. Altogether, there were 4 cases of stable disease, 2 partial responses, and 1 complete response for a disease control rate of 58%. Two of the 3 responses were at dose level 4 and the complete response was durable and had persisted for 12 months.
“Observing evidence of a dose response is extremely encouraging, and we are excited to see 2 out of 3 responses at 100 million cells/m2,” Dan Lang, MD, President,Athenex Cell Therapy, said in a statement at that time.2 “We are hopeful that we will see additional responses as we move to higher doses. We and our partners at BCM and Texas Children’s Hospital (TCH) continue to be motivated by the data and look forward to our next update.”
At the time, there were no dose-limiting toxicities seen, no immune associated neurotoxicity syndrome, and 1 case of grade 2 CRS. The trial design had originally planned to assess doses up until the sixth dose level of 1 trillion before the death occurred at the fifth dose level, but this may be amended when or ifthe trial is cleared to proceed.