Date: 2014-12-19
Type of information: Initiation of the trial
phase: 2
Announcement: initiation of the trial
Company: Innate Pharma (France)
Product: IPH2201 (anti-NKG2A antibody)
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.
Disease: squamous cell carcinoma of the oral cavity
Therapeutic area: Cancer - Oncology
Country: Germany
Trial
details: IPH2201-201 is an open label Phase II trial testing IPH2201 as a single agent in a preoperative setting of squamous cell carcinoma of the oral cavity (OCSCC), a tumor type representative of the larger group of squamous cell cancer of the head and neck. The primary objective of this trial is to evaluate the clinical and pharmacological activity of IPH2201 as a single-agent in treatment-naïve pre-operative patients with resectable intermediate or high risk (stage III-IVa) OCSCC. The secondary objectives are to assess the safety of IPH2201, the pharmacokinetics, the immunogenicity and the pharmacodynamics including intra-tumoral biomarkers. 43 patients are planned to be enrolled. The first 6 patients will receive IPH2201 at a dose of 4 mg/kg q2w x 4. Subsequent patients will be treated at a dose of 10 mg/kg q2w x 4. Based on a previous Phase I study with IPH2201, these dosages are expected to induce saturation of the NKG2A receptor. Standard loco-regional treatment with surgery followed by adjuvant therapy will be initiated after the last administration of IPH2201. Progression-free survival and survival will be assessed at 12 and 36 months after treatment administration, offering other opportunities to perform preliminary assessments of the antitumor activity.
Latest
news: * On December 19, 2014, Innate Pharma, the innate immunity company developing first-in-class therapeutic antibodies for cancer and inflammatory diseases, announced that the first Phase II trial of IPH2201, a first-in-class NKG2A checkpoint inhibitor, was opened at the Charité Comprehensive Cancer Center (CCCC), Berlin, Germany. Dr Jan D Raguse, assistant medical director, Clinic for Oral & Maxillofacial Surgery, Berlin Centre of Reconstructive Surgery, CCCC, and principal investigator of the study, said: “The rationale for this trial is based on the frequent expression of the NKG2A receptor and its ligand, HLA-E, in patients with OSCC”. The rationale of this trial is based on the expression of NKG2A by both NK and CD8+ cells infiltrating OCSCC (Katou, Ohtani et al. 2007). Binding of IPH2201 to NGK2A blocks the HLA-E driven inhibition of NK and CD8+ cells. HLA-E is expressed in about 80% of patients with squamous cell carcinoma of the head and neck (SSCHN) (Silva 2011; Nasman, Andersson et al. 2013). The resulting stimulation of both the innate and acquired immunity could lead to clinical and pharmacological antitumor activity. In a Phase I dose-escalation safety trial conducted by CCCC, IPH2201 appeared to have a safe and well-tolerated profile.
