Anti-KIR3DL2 Monoclonal Antibody for Relapsed or Refractory Cutaneous T-Cell Lymphoma
In a phase I trial reported in The Lancet Oncology, Bagot et al found that IPH4102—a first-in-class monoclonal antibody targeting KIR3DL2—was safe and showed activity in patients with relapsed or refractory cutaneous T-cell lymphoma, particularly those with Sézary syndrome. KIR3DL2 is a cell-surface protein expressed in cutaneous T-cell lymphoma, predominantly in Sézary syndrome.
The study included 44 patients treated at five sites in the United States, France, United Kingdom, and the Netherlands between November 2015 and November 2017. In the dose-escalation phase, patients received 10 dose levels of IPH4102 via intravenous infusion ranging from 0.0001 mg/kg to 10 mg/kg. In the cohort-expansion phase, patients received the selected dose weekly for the first month, every 2 weeks for the following 10 doses, and then every 4 weeks until disease progression or unacceptable toxicity. Among the 44 patients, 35 (80%) had Sézary syndrome, 8 (18%) had mycosis fungoides, and 1 (2%) had primary cutaneous T-cell lymphoma not otherwise specified.
Toxicity
In the dose-escalation phase, no dose-limiting toxicity was reported. A flat dose of 750 mg was selected for the cohort-expansion phase.
The most common adverse events were peripheral edema (in 27% of patents) and fatigue (20%), all of which were grade 1 or 2. The most common grade ≥ 3 adverse event was lymphopenia (7%), which was considered possibly treatment-related in all patients who experienced it.
Other grade 3 or 4 adverse events considered possibly related to treatment consisted of grade 4 sepsis in one patient, grade 3 aspartate aminotransferase increase in one, and grade 3 hypotension in one. One patient (who had evidence of human herpes virus 6B infection) developed fulminant hepatitis considered possibly related to treatment at 6 weeks after IPH4102 discontinuation and subsequently died.
Responses
Median follow-up was 14.1 months. Confirmed global overall response was observed in 16 patients (36%), including response in 15 (43%) of those with Sézary syndrome. Among responders with Sézary syndrome, median duration of response was 13.8 months. Median progression-free survival among patients with Sézary syndrome was 11.7 months.
The investigators concluded, “IPH4102 is safe and shows encouraging clinical activity in patients with relapsed or refractory cutaneous T-cell lymphoma, particularly those with Sézary syndrome. If confirmed in future trials, IPH4102 could become a novel treatment option for these patients. A multicohort, phase II trial (TELLOMAK) is underway to confirm the activity in patients with Sézary syndrome and explore the role of IPH4102 in other subtypes of T-cell lymphomas that express KIR3DL2.”
Martine Bagot, MD, of Hôpital Saint Louis, Paris, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Innate Pharma. For full disclosures of the study authors, visit thelancet.com.
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