Innate yo-yos after Opdivo combo data fail to wow

Innate Pharma (EPH:IPH) has posted a look at Phase I/II data on a combination of its lirilumab and Bristol-Myers Squibb’s ($BMY) Opdivo in head and neck cancer. The mix outperformed historic trials of Opdivo in isolation but by less than some hoped, causing the share price of Innate to slide then bounce back as investors digested the data.

Marseille, France-based Innate posted an interim efficacy analysis in a late-breaking abstract ahead of a presentation at the Society for Immunotherapy of Cancer Annual Meeting. The study started out escalating once-monthly doses of anti-KIR monoclonal antibody lirilumab while also administering Opdivo twice a month, before expanding the cohort after reaching the maximum dose of Innate’s experimental therapy.

Innate called the study population a “heavily pretreated, checkpoint inhibitor–naïve group” with advanced platinum refractory squamous cell carcinoma of the head and neck (SCCHN). Among the 29 evaluable patients at the time of the interim analysis, Innate saw an objective response rate of 24%. An earlier trial of single-agent Opdivo in SCCHN achieved an ORR of 13.3%. Merck’s ($MRK) rival to Opdivo, Keytruda, posted an ORR of 18% in its SCCHN study.

What that means for the future of lirilumab is unclear. If the cross-trial comparison is a fair reflection of the efficacy of the combination and monotherapies, the data suggest lirilumab makes PD-1 drugs such as Opdivo more effective in SCCHN. However, the relatively-small difference in response rates, particularly between the combination and single-agent Keytruda, raises doubts about the impact of lirilumab. Shares in Innate initially fell by up to 7%, before recovering most of the losses.

Innate and Bristol-Myers will get a clearer picture of the future of the combination in SCCHN once more data, notably overall survival readouts, start to roll in. The SCCHN study is part of a broader set of programs investigating the combination of lirilumab and Opdivo in other solid tumors and a clutch of hematological cancers. Collectively, the trials will shed light on the merit of Bristol-Myers’ decision to pay $35 million (€32 million) upfront and up to $430 million in milestones for lirilumab.

The decision and resulting trials are underpinned by a belief lirilumab can boost the effectiveness of Opdivo by blocking interactions between ligands and killer-cell immunoglobulin-like receptors (KIR). Innate thinks lirilumab can block KIR receptors and, in doing so, enable the activation of natural killer cells.