Lirilumab (IPH2102/BMS-986015) is an investigational immunotherapy being developed by Innate Pharma. The antibody is currently licensed to Bristol-Meyers Squibb (BMS) for testing in human clinical trials.
Lirilumab is being studied both alone and in combination with other cancer drugs to treat several types of solid tumors and blood cancers.
How lirilumab works
Lirilumab is a type of immunotherapy; it does not directly attack the cancer cells itself but encourages the body’s innate immune system to target and kill the abnormal cancer cells.
The immune system utilizes several types of “killer” cells to eliminate cells that are infected or abnormal. However, cancer cells frequently evade detection by mimicking signals sent by healthy cells.
Lirilumab works to help activate the immune system’s natural killer (NK) cells. NK cells have receptors that can inhibit or activate their cell-killing ability. Healthy cells express a ligand that can bind to the NK cell’s inhibitory receptors, called KIR receptors, to prevent the immune system from accidentally attacking healthy tissues. By expressing this ligand, a cancer cell can prevent the NK cell from targeting it.
Lirilumab is a monoclonal antibody, or a protein designed to target a single type of protein. It binds to the KIR receptor and blocks the interaction with its ligand found on the surface of the cancer cell. This prevents the inhibitory signal from being sent to the NK cell. But the NK cell can still recognize the activating signals produced by the cancer cell, allowing it to target and kill the tumor cell.
Lirilumab may also help activate a second type of immune cell, called a T-cell, which also attacks the cancer.
Lirilumab in clinical trials
Lirilumab is being investigated in a clinical trial program consisting of completed and ongoing clinical trials both alone and in combination with other cancer drugs.
BMS completed a Phase 1 trial (NCT01750580) called CA223-002 to assess the safety and tolerability of lirilumab in combination with Yervoy (ipilimumab) in advanced solid tumors. The results demonstrated that the treatment was well tolerated by the 22 participants, and caused no additional side effects over Yervoy therapy alone.
In the recently completed Phase 2 EFFIKIR clinical trial (NCT01687387), which evaluated lirilumab as a maintenance therapy in elderly acute myeloid leukemia (AML) patients, lirilumab did not show a clinical benefit compared to a placebo.
The double-blind randomized trial enrolled 150 patients at a number of sites in France whose AML was in remission for the first time, to receive either a high or low dose of lirilumab or a placebo.
The patients were monitored for up to two years, assessing their progression-free survival (PFS) and any adverse events. At the end of the trial, no significant difference in PFS between the lirilumab-treated patients and placebo-treated patients was recorded.
However, BMS plans to continue with the ongoing clinical trials assessing lirilumab in combination with other anti-cancer agents.
Preliminary results have been announced from a Phase 1/2 clinical trial (NCT01714739), testing lirilumab in combination with either Opdivo (nivolumab) or both Opdivo and Yervoy, in up to 650 patients with solid tumors.
Results presented in November 2016 at the Society for Immunotherapy of Cancer (SITC) 31st Annual Meeting demonstrated that the combination therapy appeared particularly effective in advanced squamous cell carcinoma of the head and neck (SCCHN) that is resistant to platinum-based chemotherapy. Out of 29 SCCHN patients, the objective response rate (ORR) was 24 percent. However, in patients with PD-L1 positive tumors (the target of Opdivo), the ORR was 41 percent.
The combination therapy showed a similar safety profile to Opdivo monotherapy. The trial is still ongoing and recruiting participants at sites across the U.S., Canada, Singapore, and Europe.
Preliminary data from an open-label Phase 2 clinical trial (NCT02399917) assessing lirilumab in combination with Vidaza (5-azacytidine) as a therapy for AML in up to 65 participants were announced at the American Society of Hematology’s (ASH) 2016 Annual Meeting in December. Results for the first 25 patients showed a response rate of 20 percent with two patients achieving complete remission (CR), where no symptoms of AML are present.
Another five trials involving lirilumab are ongoing:
- A Phase 1 trial (NCT03203876), to test the safety of lirilumab in combination with either Opdivo or Yervoy in advanced solid tumors over a two-year period, has recently started recruiting participants in Japan.
- A Phase 2 trial (NCT02481297) is ongoing to assess lirilumab in combination with Rituxan (rituximab) in patients with chronic lymphocytic leukemia (CLL) in the U.S.
- A Phase 2 trial (NCT02599649) assessing lirilumab and Opdivo in combination, with or without Vidaza, as a therapy for myelodysplastic syndromes (MDS), is recruting participants in the U.S.
- One arm of an Opdivo Phase 1 dose escalation trial (NCT01592370) is assessing lirilumab in combination with Opdivo in lymphoma and multiple myeloma (MM) patients across several sites in the U.S.
- One arm of the open-label Phase 1 Empliciti (elotuzumab) trial (NCT02252263) will also investigate the safety and efficacy of Empliciti in combination with lirilumab in myeloma patients in the U.S. and Spain.
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