The FDA has placed a partial clinical hold on investigational new drug application for lacutamab, leading to a pause in new patient enrollment for the phase 2 TELLOMAK trial and a phase 1b trial, which are evaluating the agent in patients with advanced cutaneous T-cell lymphoma and peripheral T-cell lymphoma, respectively.
The FDA has placed a partial clinical hold on investigational new drug application for lacutamab (IPH4102), leading to a pause in new patient enrollment for the phase 2 TELLOMAK trial (NCT03902184) and a phase 1b trial (NCT05321147), which are evaluating the agent in patients with advanced cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), respectively.1
The decision was made after an unexpected, severe adverse effect (AE) was reported. One patient experienced a fatal case of hemophagocytic lymphohistiocytosis.
Patients who are already receiving treatment and deriving clinical benefit on either trial are allowed to continue treatment after renewed consent.
“Patient safety is of paramount importance to us, and we are currently undertaking efforts to address the FDA requests, which include incorporation of risk mitigation and management strategies for hemophagocytic lymphohistiocytosis in ongoing lacutamab studies,” Mondher Mahjoubi, chief executive officer of Innate Pharma, stated in a news release. “Additionally, with all patients recruited into the phase 2 TELLOMAK study, we do not currently anticipate any delay for the TELLOMAK phase 2 final data due shortly.”
Lacutamab is a first-in-class, anti-KIR3DL2 humanized cytotoxicity-inducing antibody being investigated for the treatment of patients with CTCL and PTCL.
TELLOMAK is a global, open-label, multi-cohort, multicenter trial evaluating the agent in patients with relapsed/refractory stage IVA/B CTCL who have received at least 2 prior systemic therapies, including mogamulizumab-kpkc (Poteligeo).2
The trial includes the following cohorts:
All patients are being treated with 750 mg of lacutamab once per week for 5 weeks, then once every 2 weeks for 10 doses, then once every 4 weeks until disease progression or unacceptable toxicity.
Objective response rate is serving as the trial’s primary end point. Secondary end points include safety, quality of life, progression-free survival, overall survival, and pharmacokinetics.
TELLOMAK is fully enrolled, and final data are expected in the fourth quarter of 2023.
The phase 1b trial is evaluating single-agent lacutamab in patients with relapsed/refractory PTCL that expresses KIR3DL2 who received at least 2 cycles of at least 1 prior line of treatment. A KIR3DL2 expression of at least 1% per immunohistochemistry based on central evaluation is required. Other key inclusion criteria include at least 1 target lesion on PET/CT scan at screening, an ECOG performance status of 0 to 2, and adequate laboratory data.3
All patients in the phase 1b study are also receiving 750 mg of lacutamab once per week for 5 weeks, then once every 2 weeks for 10 doses, then once every 4 weeks until disease progression or unacceptable toxicity.
The trial’s primary end point is the frequency of AEs.
A futility interim analysis is awaited for the phase 1b study, and preliminary data are expected in the fourth quarter of 2023.