Date: 2016-11-30
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium
Company: Innate Pharma (France) the Canadian Cancer Trials Group (CCTG) (Canada)
Product: monalizumab (IPH2201)
Action
mechanism: monoclonal antibody/immune checkpoint inhibitor. Monalizumab (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: ovarian cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On November 30, 2016, Innate Pharma announced preliminary safety results from the dose-ranging part of a Phase I/II trial investigating monalizumab as a single agent in patients with advanced gynecologic malignancies. The data have beeen presented as a poster at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium (Munich, Germany) and have been discussed by Dr Anna Tinker, Medical Oncologist (British Columbia Cancer Agency, Vancouver) on behalf of CCTG. The trial is sponsored and conducted by the Canadian Cancer Trials Group (CCTG). In this dose-ranging part of the study, 18 patients with advanced, heavily pretreated ovarian cancer were randomized to receive three dose levels of monalizumab (1, 4 and 10 mg/kg, every two weeks – six patients at each dose level). The data showed that monalizumab was well tolerated in this patient population, with no dose-limiting toxicities observed. No major differences in terms of safety were observed across the different dose levels. The most common adverse events (AEs) reported include fatigue and headaches. AEs were mostly low grade and rarely resulted in treatment delays. Preliminary efficacy data showed short-term disease stabilization in 41% of patients, including one patient with a mixed response. Pierre Dodion, Chief Medical Officer of Innate Pharma, said: “These are the first clinical data reported with monalizumab in cancer patients and they suggest a favorable safety profile. Preliminary results support the continuation of the ongoing cohort expansion part of this study and we look forward to its results. A comprehensive exploratory clinical plan investigating monalizumab in several indications, as both a monotherapy and combination treatment, is underway. We look forward to reporting further data as we move into 2017.” The cohort expansion part of this trial (up to 98 patients) is ongoing at the recommended Phase II dose (10 mg/kg) in patients with platinum sensitive ovarian cancer, platinum-resistant ovarian cancer, epithelial endometrial cancer and squamous cell carcinoma of the cervix.
