French clinical-stage biotechnology company Innate Pharma has reported positive data from its dose-ranging part of a Phase I/II trial of monalizumab to treat advanced gynecologic malignancies.

Monalizumab is a humanised IgG4 inhibiting NKG2A from binding to HLA-E allowing activation of NK and cytotoxic T-cell responses.

Blocking of the inhibitory NKG2A receptors, monalizumab induces a pronounced anti-tumour response mediated by NK and T-cells. It can also enhance cytotoxic potential of other therapeutic antibodies.

Sponsored and conducted by the Canadian Cancer Trials Group (CCTG), the Phase I/II open-label, dose escalation trial is assessing monalizumab as a single agent to treat 98 patients with gynecologic malignancies.

The secondary goals of the trial are to test safety, pharmacokinetics, pharmacodynamics and immunogenicity of monalizumab.

During the first part of the trial, the patient will receive 1mg/kg, 4mg/kg or 10mg/kg of monalizumab every two weeks and in the second part of the trial, patients will receive the recommended phase II dose (RP2D).

"Monalizumab was well tolerated in this patient population with advanced gynecologic malignancies."

The dose-ranging part of the study examined 18 patients with advanced, heavily pretreated ovarian cancer who received three dose levels of monalizumab.

Results suggested that monalizumab was well tolerated among patients with no dose-limiting toxicities.

Preliminary efficacy data has also suggested short-term disease stabilisation in 41% of patients.

CCTG Investigational New Drug Programme director Lesley Seymour said: “Monalizumab was well tolerated in this patient population with advanced gynecologic malignancies.

“These refractory tumours are an area of unmet need, and are typically treated with cytotoxic chemotherapy that is often poorly tolerated.

“Building on these initial results, further investigation of monalizumab in these patients is warranted and we are therefore continuing to enrol patients with relapsed and refractory gynecologic malignancies into the expansion phase of the study.”

The cohort expansion of this trial is currently being undertaken at the recommended Phase II dose (10mg/kg) in patients with platinum sensitive ovarian cancer, platinum-resistant ovarian cancer, epithelial endometrial cancer and squamous cell carcinoma of the cervix.