FDA Puts Innate’s Lymphoma Trials on Partial Hold After Patient Death
Pictured: FDA headquarters/iStock, Grandbrothers
According to Innate’s announcement, the patient died due to hemophagocytic lymphohistiocytosis, a rare blood condition characterized by excessive immune activation leading to the pathological build-up of certain white blood cells in organs such as the liver and spleen.
The partial clinical hold prevents new enrollment in the Phase II TELLOMAK study, which is assessing lacutamab in cutaneous T-cell lymphoma (CTCL), and a Phase Ib trial in peripheral T-cell lymphoma. Patients who are already receiving lacutamab and are seeing clinical benefit may continue their treatment after reconsenting, according to Innate.
The company is currently addressing the FDA’s requests in connection with the fatality and the studies’ safety, “which include the incorporation of risk mitigation and management strategies for hemophagocytic lymphohistiocytosis in ongoing lacutamab studies,” Innate CEO Mondher Mahjoubi said in a statement.
In addition, because TELLOMAK has already completed its enrollment, Innate does not anticipate the clinical hold to delay the study’s final data readout, Mahjoubi said.
The initial cohort of the Phase Ib trial is also fully enrolled and the study is currently awaiting an interim analysis to determine if it can proceed to the next stage.
Thursday’s clinical hold is the second regulatory pause for TELLOMAK. In late 2019, the FDA halted enrollment into the study, citing issues at a subcontractor’s manufacturing site. At the time, the regulator did not identify safety issues associated with lacutamab and allowed patients already participating in the study to continue treatment after reconsenting.
The manufacturing issues also convinced other countries to place their own regulatory freezes on TELLOMAK, including the U.K. and France. Innate voluntarily suspended enrollment for the study in December 2019.
In June 2020, the FDA lifted its partial clinical hold after conducting quality assessments on a batch of lacutamab to be used for the clinical development program.
Lacutamab is a humanized, cytotoxicity-inducing antibody that works by targeting the KIR3DL2 receptor. KIR3DL2 is an inhibitory receptor belonging to the KIR family and is expressed by around 65% of CTCL patients across all cancer subtypes. Its prevalence shoots up to 90% in certain aggressive CTCL subtypes but its expression in normal tissues is restricted.