Clinical Trials

Date: 2017-11-22

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 59th American Society of Hematology (ASH) Annual Meeting

Company: BMS (USA - NY) Innate Pharma (France)

Product: lirilumab or IPH2102/BMS-986015

Action mechanism:

• monoclonal antibody/immune checkpoint inhibitor. Lirilumab or IPH2102/BMS-986015 is a fully human monoclonal antibody blocking interaction between Killer-cell immunoglobulin-like receptors (KIR) on NK cells with their ligands. Blocking these receptors facilitates activation of NK cells and, potentially, destruction of tumor cells by the latter.
• IPH2102/BMS-986015 is licensed to BMS. As part of the agreement between Innate Pharma and BMS, BMS holds exclusive worldwide rights to develop, manufacture and commercialize IPH2102/BMS-986015 and related compounds blocking KIR receptors, for all indications. Under the agreement, Innate Pharma will complete the development of IPH2102 through Phase II in AML.

Disease: acute myeloid leukemia (AML)

Therapeutic area: Cancer - Oncology

Country: France

Trial details:

• EffiKIR is a double-blind placebo-controlled randomized Phase II trial of IPH2102/BMS-986015 as maintenance treatment in elderly patients with acute myeloid leukemia (AML) in first complete remission. The protocol calls for inclusion of 150 patients, randomized into three arms. Two arms will test single agent IPH2102/BMS-986015 at different doses and one arm will receive placebo. The primary efficacy endpoint is leukemia-free survival. Secondary endpoints include safety and overall survival. The rationale of this trial is based on the capacity of activated Natural Killer (NK) cells to directly kill tumor cells and trigger a broad immune activation. This rationale is supported by clinical studies showing that activated NK cells may significantly lower the recurrence of various hematological malignancies, including AML, following hematopoietic stem cell transplantation. This trial is performed in France, with the participation of the two French clinical cooperative groups, ALFA and GOELAMS, harnessing the research effort of the French centers qualified to treat patients with AML. (NCT01687387)

Latest news:

• • On November 22, 2017, Innate Pharma provided an update on the clinical study program of lirilumab, licensed to BMS. Full data from the previously disclosed Phase II EffiKIR trial testing lirilumab as a single agent maintenance treatment in elderly patients with acute myeloid leukemia will be discussed at the upcoming ASH Annual Meeting 2017 in an oral presentation on December 11, by the principal investigator Pr. Norbert Vey, Team leader Translational Medicine – Hematology at the Paoli-Calmettes Institute (IPC). These data suggest that alternate dosing regimens, where KIR receptors are not permanently occupied and allow the interaction with their cognate ligands during maturation, could be worth exploring.
• • On February 6, 2017, Innate Pharma announced top-line results from the EffiKIR trial. The study did not meet its primary efficacy endpoint of leukemia-free survival (LFS). Two arms of the trial tested single agent lirilumab at different doses and treatment intervals (0.1 mg/kg q3months or 1 mg/kg q1month) whereas in the third arm, patients received placebo. There was no statistically significant difference between either lirilumab arms and the placebo arm on the LFS nor on other efficacy endpoints. As announced in March 2015, one arm of the trial was discontinued upon DSMB recommendation. This arm has now been identified as the 1 mg/kg q1month arm of the trial. At the time of its decision, the DSMB assessed that the objective of achieving a superior LFS in this arm compared to placebo could not be reached. There was no concern with tolerance. Data analyses are ongoing and the full trial data will be submitted to a future medical conference and for publication. • On September 29, 2016, Innate Pharma announced that the Data and Safety Monitoring Board completed its seventh assessment of the EffiKIR study and recommended continuation of the trial without modification. Enrolment in the EffiKIR study was completed in July 2014. The analysis on the primary endpoint, leukemia-free survival, is event driven and could occur by the end of 2016.
• • On March 26, 2015, Innate Pharma announced that the Data and Safety Monitoring Board completed its fourth assessment of the EffiKIR study and recommended to stop treatment in one arm and continue the trial with the remaining two arms as per protocol. In issuing this recommendation, the DSMB considers that treatment in the stopped arm cannot be superior to placebo. There is no concern with safety. Patients in the stopped arm will be followed up as planned. The trial remains blinded. • On September 25, 2014, Innate Pharma announces that the Data and Safety Monitoring Board (“DSMB”) completed its third assessment of the EffiKIR study and recommended continuation of the trial, as planned. Enrolment in the EffiKIR study was completed in July 2014 and data on the primary endpoint, Leukemia-Free Survival, are expected end of 2015.
• • On July 24, 2014, Innate Pharma announced completion of target enrollment in the EffiKIR trial with 150 patients randomized. Results of this Phase II trial of lirilumab as maintenance treatment in elderly patients with acute myeloid leukemia (AML) in first complete remission are expected by the end of 2015.
• • On March 12, 2014, Innate Pharma has announcee that the Data and Safety Monitoring Board (“DSMB”) completed its second assessment of the EffiKIR study and recommended continuation of the trial, as planned.
• As specified in the study protocol, the DMSB meets periodically to examine the safety data accumulated during progress of the trial. Enrolment in the study is on track, with more than 100 patients included.
• • On September 17, 2013, Innate Pharma has announced that the Data and Safety Monitoring Board (“DSMB”) completed its first assessment of the EffiKIR study and unanimously recommended continuation of the trial without modification. The assessment was based on a safety analysis pre-planned for when the first 30 patients would be treated with a minimum of two cycles of therapy.
• • On May 28, 2013, Innate Pharma has announced that three posters on lirilumab (IPH2102/BMS-986015) will be presented at the ASCO (American Society of Clinical Oncology) 13th annual meeting, in Chicago, Illinois, May 31-June 4, 2013. “Intergroup ALFA/GOELAMS randomized phase II trial of lirilumab anti-KIR monoclonal antibody (IPH2102/BMS986015) as maintenance treatment in elderly patients with acute myeloid leukemia (EFFIKIR trial)”.
• • On December 17, 2012, Innate Pharma has announced that the first patient was treated in the EffiKIR trial. Last september, the company has received regulatory authorization to initiate this trial. IPH2102/BMS-986015 is also currently tested in a Phase I trial in combination with the anti-PD-1 antibody nivolumab (BMS-936558) in solid tumors.
• • On September 4, 2012, Innate Pharma has announced that it has received regulatory authorization to start a double-blind placebo controlled randomized Phase II trial of IPH2102/BMS-986015 as maintenance treatment in elderly patients with Acute Myeloid Leukemia (AML) in first complete remission (study IPH2102-201, the “EffiKIR” trial). The rationale of this trial is based on the capacity of activated Natural Killer (NK) cells to directly kill tumor cells and trigger a broad immune activation. This rationale is supported by clinical studies showing that activated NK cells may significantly lower the recurrence of various hematological malignancies, including AML, following hematopoietic stem cell transplantation. This trial is sponsored by Innate Pharma and will be performed in France, with the participation of the two French clinical cooperative groups, ALFA and GOELAMS, harnessing the research effort of the French centers qualified to treat patients with AML. First patient inclusion is expected before the end of the year.

 

Is general: Yes