Innate hopes dosing tweak will save BMS-partnered lirilumab

Innate Pharma has admitted that it can’t see an obvious way to bring its cancer antibody lirilumab forward in development after it flunked a second clinical trial.

The French biotech has revealed the combination of lirilumab and Bristol-Myers Squibb’s PD-1 inhibitor Opdivo (nivolumab) failed to show any additional benefit compared to Opdivo alone in patients with squamous cell carcinoma of the head and neck (SCCHN) ahead of the Thanksgiving break, sending its shares into steep decline.

That disappointment comes in the wake of a failed phase 2 trial in which the anti-killer cell immunoglobulin-like receptor (KIR) antibody was unable to improve progression-free survival (PFS) compared to placebo in elderly patients with acute myeloid leukemia (AML).

A trio of disappointing trials put the future of the drug—partnered with BMS in an up-to-$465 million deal inked in 2011—firmly in doubt, although Innate isn’t ready to call time on the program just yet, saying it is still in negotiations with its partner.

It thinks there may be a lifeline for lirilumab in a new analysis of the AML trial data which suggests alternative dosing regimens in which the drug is delivered on an intermittent rather than continuous basis could improve efficacy. In essence.

Targeting KIRs, found on natural killer cells, is intended to rev up the ability of the immune system to seek out and destroy malignant cells. Innate’s latest idea is that continual blockade of KIR isn’t the best way to go about that because it could interfere with the functioning of NK cells.

It will have an opportunity to gauge the reaction to that hypothesis when it presents updated data from the AML study at the American Society of Hematology (ASH) meeting in Atlanta next month.

“We remain convinced, based on broad preclinical evidence, that NK cells play an important role in cancer immunosurveillance,” said Innate’s CEO Mondher Mahjoubi.

“Together with [BMS] we will further examine these data to better understand the results and explore whether other combinations should be investigated.”

If Innate and BMS can’t see a way to advance lirilumab, Innate will have to turn its attention to monalizumab, a CD94/NKG2A-targeting immuno-oncology candidate heading for mid-stage testing as a monotherapy and in combination with AstraZeneca’s PD-L1 inhibitor Imfinzi (durvalumab) in a range of solid tumors and blood cancers, and anti-KIR3DL2 IPH4102 for lymphomas in phase 1.