Date: 2015-10-06
Type of information: Initiation of the trial
phase:
Announcement: initiation of the trial
Company: Innate Pharma (France) AstraZeneca (UK)
Product: IPH2201 (anti-NKG2A antibody) and ibrutinib
Action
mechanism: monoclonal antibody/immune checkpoint inhibitor. IPH2201 (anti-NKG2A) is a first-in-class humanized IgG4 antibody. NKG2A is a checkpoint receptor that inhibits anti-cancer functions of cytotoxic NK and T lymphocytes. NKG2A recognises HLA-E ligands, and by expressing HLA-E cancer cells can protect themselves from killing by CD94/NKG2A-positive NK-, NKT-, and T-cells (a/b and g/d). HLA-E is frequently up-regulated on cancer cells and this occurs in patients with different types of solid tumours or haematological malignancies. In some types of cancers, high-levels of HLA-E appear to confer poorer prognosis. IPH2201 blocks the inhibitory function of CD94/NKG2A, thereby unleashing NK and T cells to kill cancer cells, despite expression of HLA-E. IPH2201 enhances NK and T cell killing of a variety of cancer cell types. Hence, IPH2201 may potentially re-establish a broad anti-tumour response mediated by NK and T cells. Anti-NKG2A mAb may also enhance the cytotoxic potential of other therapeutic antibodies. In an ongoing single- and multiple-dose Phase I dose-escalation safety trial in patients with rheumatoid arthritis, IPH2201 appears to have a safe and well-tolerated profile at all doses tested. Bruton tyrosine kinase inhibitor. Ibrutinib is a novel Bruton’s tyrosine kinase (BTK) inhibitor being jointly developed by Janssen and Pharmacyclics, Inc. for the treatment of B-cell malignancies. Ibrutinib is jointly developed and commercialized in the United States by Pharmacyclics and Janssen Biotech, Inc. In Europe, Janssen-Cilag International NV (Janssen) holds the marketing authorization and its affiliates market Imbruvica® in EMEA (Europe, Middle East, Africa), as well as the rest of the world. Imbruvica® is already approved in Europe to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL) and adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy or in first line use in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy. In March 2015, Abbvie and Pharmacyclics announced a definitive agreement under which AbbVie will acquire Pharmacyclics, and its flagship asset Imbruvica® (ibrutinib).
Disease: relapsed or refractory chronic lymphocytic leukemia
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The phase 1b/2a IPH2201-202 study is a multicenter open label trial of the combination of IPH2201 and ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia. Its primary objective is to evaluate the anti-leukemic activity of the combination and the primary endpoint for efficacy is complete response rate. The secondary objectives are to assess the safety of the combination of IPH2201 and ibrutinib. The trial will be performed in the United States under the coordination of leading investigators at the Ohio State University.36 to 45 patients are planned to be enrolled. The trial is conducted in two parts: - In the first part of the study, 12 to 24 patients will receive a combination of ibrutinib at the approved dosage and IPH2201; 4 dose levels of IPH2201 up to 10 mg/kg will be explored. Based on previous experience with IPH2201, these dosages are expected to induce saturation of the NKG2A receptor. - In the second part of the study, IPH2201 at the dose selected in the dose-escalating part will be assessed in combination with ibrutinib during 26 cycles in up to 24 patients. The rationale of this trial is based on the observation that HLA-E is expressed in virtually all patients with CLL, at higher levels compared to normal B cells (Veuillen, Aurran-Schleinitz et al. 2012). IPH2201 is a NGK2A checkpoint inhibitor that blocks the HLA-E driven inhibition of NK and CD8+cells. By binding to NGK2A, IPH2201 restores the capability of those cells to destroy tumor cells. Furthermore, ibrutinib has been demonstrated to create a favorable pro-inflammatory environment; this could result in a synergistic effect with the immunotherapeutic action of IPH2201.Thus, treatment with IPH2201 in combination with ibrutinib may improve the quality of response above and beyond that achieved with ibrutinib alone and achieve complete responses; a higher rate of complete response should lead to improved overall survival.
Latest
news: * On October 6, 2015, Innate Pharma announced the opening of the Phase I/II trial of IPH2201, a first-in-class NKG2A checkpoint inhibitor, tested in combination with ibrutinib in patients with relapsed or refractory Chronic Lymphocytic Leukemia (\"CLL\"). This trial, which will include up to 45 patients, is multicentric and will be performed in the United States. This trial is part of a global co-development and commercialization agreement with AstraZeneca for IPH2201. Within this frame, Innate Pharma expects to have four trials opened by the end of 2015. In addition to the CLL trial, two Phase I/II studies are currently ongoing, testing IPH2201 as a single agent respectively in squamous cell carcinoma of the Head and Neck and in Ovarian cancer. The fourth trial, testing IPH2201 in combination cetuximab in patients with Head and Neck cancer, will start in the coming months.
