Date: 2015-09-28
Type of information: Treatment of the first patient
phase: 1-2
Announcement: treatment of the first patient
Company: NCIC Clinical Trials Group (Canada) 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: ovarian Cancer, Fallopian tube cancer, peritoneal cancer
Therapeutic area: Cancer - Oncology
Country: Canada
Trial
details: This dose-ranging study of IPH2201 in patients with high grade serious carcinoma of ovarian, Fallopian tube or peritoneal origin will test the safety of aIPH2201, to see what effects it has on this type of cancer. This Phase I/II trial is an open-label, multicentre, dose ranging study of single agent IPH2201 administered i.v. every 2 weeks in patients with advanced/metastatic/recurrent platinum sensitive or resistant high-grade serous carcinoma of ovarian, fallopian tube or peritoneal origin. In the first part of the study, a total of 18 patients (6/dose level) will be randomized to one of 3 dose levels: 1 mg/kg, 4 mg/kg and 10 mg/kg. The recommended Phase II dose (RP2D) will be determined based on toxicity, pharmacokinetics and pharmacodynamics data.
Thereafter, a total of 20 patients (10/cohort) will be registered to two cohorts (platinum sensitive or resistant) and will receive IPH2201 at the RP2D, as determined in Part 1 above. The objectives of the second part of the trial are to perform a preliminary assessment of the efficacy (measured by the response rate) of IPH2201, as well as of its safety, pharmacokinetics, pharmacodynamics and immunogenicity. Many patients with ovarian cancer suffer from ascites, which will allow documentation of the pharmacological effects of IPH2201.
The rationale of the trial is based on the frequent (approximately 70 to 80% of the patients) upregulation of HLA-E, the ligand of NKG2A, in ovarian cancer (Gooden, OncoImmunol, 2012). Furthermore, HLA-E overexpression is a poor prognostic factor in gynecologic tumors (Gooden,PNAS, 2011). Additionally, the presence of tumor-infiltrating lymphocytes correlates with improved
outcome (Zhang, N Engl J Med, 2003; Sato, PNAS, 2005) especially in those cancers with high HLA-E expression (Gooden, PNAS, 2011). Binding of IPH2201 to NGK2A blocks the HLA-E driven inhibition of NK and CD8+ cells. Thus, treatment with IPH2201 may stimulate both innate and acquired immunity that could lead to clinical and pharmacological antitumor activity. In a Phase I dose-escalation safety trial, IPH2201 was found to have a safe and well-tolerated profile. (NCT02459301)
Latest
news: * On September 28, 2015, Innate Pharma announced that the first patient was treated in the Phase I/II trial testing IPH2201 as a single agent in platinum resistant or sensitive patients with high grade ovarian cancer. Thirty-eight (38) patients are planned to be enrolled. This is the second out of four trials announced by Innate Pharma, included in the frame of the global co-development and commercialisation agreement signed with AstraZeneca for IPH2201 in April 2015. The first trial (IPH2201-201) is an open label Phase II trial testing IPH2201 as a single agent in a pre-operative setting of squamous cell carcinoma of the oral cavity (OCSCC). * On March 9, 2015, Innate Pharma announced that investigators from NCIC Clinical Trials Group presented the rationale and protocol of the Phase I/II trial of IPH2201, a first-inclass NKG2A checkpoint inhibitor, as a single agent in platinum resistant or sensitive patients with high grade ovarian cancer at the 13th International Congress on Targeted Anticancer Therapies. NCIC CTG is sponsoring the study (known as IND.221) which will be conducted in Canada and enroll patients with ovarian cancer. In the first part of the study patients will receive IPH2201 at one of three dose levels. Thereafter 20 additional patients will be enrolled, in two groups, including patients whose ovarian cancer is felt to be either platinum sensitive or resistant.
The first patient was treated at the Charité Comprehensive Cancer Center (CCCC), Berlin, Germany, in December 2014.
As part of Innate’s program, two further trials, testing IPH2201 in combination with ibrutinib in patients with Chronic Lymphocytic Leukemia, and with cetuximab in patients with Head and Neck cancer, will start in 2015. The initial development plan also includes Phase II combination clinical trials with IPH2201 and durvalumab (MEDI4736), an anti-PD-L1 immune checkpoint inhibitor, in solid tumors, which will be performed by AstraZeneca.
