BMS, Innate checkpoint inhibitor flunks AML phase 2

Lirilumab failed to beat placebo against any efficacy endpoint.

A phase 2 trial of Innate Pharma’s lirilumab in elderly patients with acute myeloid leukemia (AML) has missed its primary endpoint. The Bristol-Myers Squibb-partnered checkpoint inhibitor failed to improve leukemia-free survival by more than placebo.

Innate enrolled 150 people in the trial and randomized them to receive one of two doses of the anti-KIR monoclonal antibody or a placebo. The clinical trial failed to find a statistically significant difference between either treatment arm and the placebo in terms of leukemia-free survival or any other efficacy endpoint. The across-the-board failure is a stumble at the first major clinical efficacy hurdle faced by lirilumab.

“Although we knew that this setting was challenging, we are disappointed by the results of the EffiKIR study and will investigate further to better understand the data in its entirety,” Innate Chief Medical Officer Pierre Dodion said in a statement.

The first hint that lirilumab could come up short arrived when the Data and Safety Monitoring Board (DSMB) completed its fourth review of the study in March 2015. At that time, the DSMB recommended stopping treatment in one of the arms as it was already unable to beat placebo. In unblinding the study, Innate has revealed the DSMB recommended stopping the higher of the two doses, dispelling earlier assumptions that the lower dose was more likely to struggle.

That finding and the other results of the phase 2 AML trial raise doubts about the odds of success in the suite of studies set up by Bristol-Myers and Innate. Since paying Innate $35 million (€33 million) for the rights to lirilumab, Bristol-Myers has kicked off a clutch of trials to test the anti-KIR monoclonal antibody in combination with drugs including its PD-1 drug Opdivo.

Innate is clinging to interim phase 1/2 results suggesting lirilumab boosts the efficacy of Opdivo in patients with squamous cell carcinoma of the head and neck as evidence of the potential of its asset as it heads toward a critical series of data readouts.

“EffiKIR is only one of seven studies currently investigating lirilumab. Lirilumab is tested in a broad and comprehensive combination program in multiple indications and we saw encouraging early efficacy signals of lirilumab in combination with nivolumab at the 2016 SITC meeting. We are looking forward to the next data sets as well as the next steps for the program in 2017,” Dodion said.

Bristol-Myers initiated the combination trials to test the idea that targeting KIR and PD-1 will deliver better outcomes than going after the latter pathway alone. While Opdivo blocks the inhibitory effect of PD-1 receptors on T cells, lirilumab is designed to stop KIR2DL-1,-2,-3 inhibitory receptors from interacting with their ligands. Together, the drugs have the potential to unleash T cells and natural killer cells at tumors, resulting in greater efficacy than Opdivo alone.

Clinical trial data backing up the theory would deliver a boost to Bristol-Myers, which is rocking from setbacks in the clinic and seeking an edge over Merck’s Keytruda and other PD-1/PD-L1 drugs that are set to start challenging for the market.

Shares in Innate opened down 23% in Paris.