Innate lymphoma trials put on partial hold after patient dies, but fully enrolled phase 2 stays on track

Innate Pharma’s lymphoma program has hit a safety snag, with the FDA imposing a partial clinical hold on studies after a patient died of a rare hematologic disorder. The biotech remains on course to report data from its two fully enrolled trials but saw its stock drop in the aftermath of the safety signal.

The partial clinical hold applies to lacutamab, an anti-KIR3DL2 antibody that Innate is studying in patients with cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). Innate sees lacutamab, also known as IPH4102, as a first-in-class prospect that could improve lymphoma outcomes by depleting cells that express KIR3DL2, a receptor that is widely found in forms of the blood cancer.

In working to validate that idea, Innate has seen a fatal case of hemophagocytic lymphohistiocytosis (HLH). The severe systemic inflammatory syndrome can happen when the immune system is activated strongly, such as when it is fighting cancer. In other patients, the condition has a genetic cause. 

Innate has shared little information about what happened in the trial, only revealing that a patient died after an unexpected severe adverse reaction, namely HLH. The death led the FDA to place a partial hold on studies of lacutamab and ask Innate to take steps to mitigate the risk.

“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,” Innate CEO Mondher Mahjoubi, M.D., said in a statement.

The partial hold prevents Innate from enrolling new patients in lacutamab trials but allows it to continue dosing existing participants who are deriving clinical benefit. Because the phase 2 CTCL trial, and the initial cohort of a phase 1 PTCL study, are already fully enrolled, the partial hold should have minimal impact on near-term timelines. Innate is still on track to share final phase 2 and preliminary phase 1 data this year.

While no delay to the phase 2 readout is anticipated, Innate has taken much longer than expected to get to this point. A phase 1 clinical trial of lacutamab began in 2015. That study was originally scheduled to reach primary completion in 2018 but ultimately wrapped up in 2020. The primary completion date of the phase 2 trial that is set to post final data soon slipped, too, going from March 2022 to October 2023. 

Shares in Innate fell 8.5% to 2.30 euros in early trading in Paris.