About this program

Lirilumab (IPH2102/BMS-986015) is a fully human monoclonal antibody that is designed to block the interaction between KIR2DL-1,-2,-3 inhibitory receptors and their ligands.

Blocking these receptors facilitates activation of NK cells and, potentially some subsets of T cells, ultimately leading to destruction of tumor cells.

Lirilumab has been or is currently being tested in several indications and combination settings.

In the fourth quarter of 2016, several sets of clinical data on lirilumab were presented at scientific meetings (visit the clinical development section for more information, posters available in the documents section).

The mechanism behind NK cells activation depends on a balance between activatory and inhibitory signals, ie. signals of abnormality sent by the target:

  • Normal cells send “normality” signals and are thus spared by NK cells;
  • Cells undergoing a stress (infection, cancerous transformation, over activation) can send normality as well as danger signals at the same time. This can result in the “blinding” of NK cells.

Lirilumab, an anti-KIR monoclonal antibody, aims at “unblinding” NK cells and facilitating their activation by blocking their inhibitory receptors.  

Lirilumab and related compounds blocking KIR receptors are licensed to Bristol-Myers Squibb Company (NYSE:BMY), for all indications.

Innate Pharma received an upfront payment of $35 million at the signing of the agreement in July 2011. The Company is eligible to additional payments of up to $430 million, depending on the achievement of pre-specified milestones during the development and commercialization period, as well as pre-specified tiered double-digit royalty payments on worldwide net sales.

Bristol-Myers Squibb funds the development of lirilumab and Innate Pharma provides preclinical support to the program.

A broad exploratory clinical program is ongoing, investigating lirilumab in combination with other agents, in solid tumors and hematological malignancies:





Combination nivolumab and nivolumab + ipilimumab

Phase I/II with dose escalation and cohort expansion

Selected solid tumors including SCCHN (randomized part)

Up to 650 patients*

Started October 2012

Safety data at ESMO 2016

Preliminary efficacy data at SITC 2016

Combination nivolumab

Phase I with dose escalation

Lymphoma and multiple myeloma

Up to 315 patients**

Started October 2014

Combination elotuzumab

Phase I with dose escalation and  randomized cohort expansion

Multiple Myeloma: R/R MM

or post autologous transplant

Up to 136 patients***

Started October 2014

Combination 5-azacytidine (Vidaza)

Phase II with dose escalation

Acute Myeloid Leukemia


Up to 64 patients

Started April 2015

Preliminary data at ASH 2016

Combination rituximab

Phase II

Chronic Lymphocytic Leukemia

R/R or High-risk Untreated

Up to 48 patients

Started June 2015

Combination nivolumab and 5-azacytidine

Phase II

Myelodysplastic Syndromes

Up to 80 patients

Started November 2015

* (nivolumab, lirilumab + nivolumab, lirilumab + nivolumab + ipilimumab)

** Three arms (nivolumab, nivolumab + ipilimumab, nivolumab + lirilumab)

*** Two arms (elotuzumab + lirilumab, elotuzumab + urelumab)

NK cells (Natural Killer) are non conventional lymphocytes, belonging to the innate immunity compartment. They are able to:

  • Directly and selectively kill « stressed » cells (cancerous, infected or over-activated cells);
  • Participate in the set up of a global immune reaction against a selected target, notably via the production of cytokines (the communicating agents of the immune system)
  • Bind one of the two ends of cytotoxic antibodies, and then kill cells recognized by these antibodies. This property is known as antibody-dependent cellular cytotoxicity (ADCC)


ASH 2016: Phase IB/II Study of Lirilumab in Combination with Azacytidine (AZA) in Patients with Relapsed Acute Myeloid Leukemia384.97 KB
SITC 2016 : Late-breaking presentation on Interim Phase 1/2 Data for Lirilumab in Combination With Nivolumab1.58 MB
ESMO 2016: Safety of Lirilumab in Combination With Nivolumab or Ipilimumab in Two Phase 1 Studies in A/R Solid Tumors546.76 KB
ASCO 2015: A phase 1 dose-escalation study of lirilumab in patients with various hematologic or solid malignancies636.4 KB
ASH 2014: Lirilumab Enhances Anti-Tumor Efficacy of Elotuzumab236.48 KB
ASH 2014: Effects of IL-21, KIR Blockade, and CD137 Agonism on the Non-Clinical Activity of Elotuzumab1.62 MB
ASCO 2014 (BMS) : A Phase 1 Study of Lirilumab Administered in Combination With Nivolumab in Advanced Solid Tumors3.91 MB
ASH 2013: Repeated Dosing Of Anti-KIR (IPH2101) As Maintenance Therapy In Elderly Patients With Acute Myeloid Leukemia279.68 KB
ASH 2013: A Phase I Trial Of Anti-KIR Monoclonal Antibody IPH2101 and Lenalidomide For Multiple Myeloma527.81 KB
ASH 2013: Anti-KIR antibody enhancement of anti-lymphoma activity of NK cells as monotherapy and in combination with anti-CD20401.35 KB
ASCO 2013: ALFA/GOELAMS Randomized Phase II Trial of Lirilumab as Maintenance Treatment in Elderly Patients with AML622.3 KB
ASCO 2013 (BMS): A Phase I Study of Lirilumab (BMS-986015), an Anti-KIR Monoclonal Antibody, Administered with Ipilimumab...2.59 MB
ASCO 2013 (BMS): A Phase I Dose-escalation and Cohort Expansion Study of Lirilumab Administered in Combination With Nivolumab1.88 MB
AACR 2013: Anti-tumoral efficacy of therapeutic human anti-KIR antibody (lirilumab) in a preclinical xenograft tumor model291.36 KB
ASH 2009: A Phase I Study of the Anti-Natural Killer Inhibitory Receptor (KIR) Monoclonal Antibody (IPH2101) in Elderly Patient61.11 KB